diff --git a/mypy/subtypes.py b/mypy/subtypes.py
index cb630c68b62a..49689db7ea41 100644
--- a/mypy/subtypes.py
+++ b/mypy/subtypes.py
@@ -547,8 +547,7 @@ def f(self) -> A: ...
             return False
     assuming = right.type.assuming_proper if proper_subtype else right.type.assuming
     for (l, r) in reversed(assuming):
-        if (mypy.sametypes.is_same_type(l, left)
-                and mypy.sametypes.is_same_type(r, right)):
+        if l == left and r == right:
             return True
     with pop_on_exit(assuming, left, right):
         for member in right.type.protocol_members:
diff --git a/mypy/test/testtypes.py b/mypy/test/testtypes.py
index e9e169ccc84e..0600c333944d 100644
--- a/mypy/test/testtypes.py
+++ b/mypy/test/testtypes.py
@@ -1055,6 +1055,7 @@ def setUp(self) -> None:
         self.fx = TypeFixture()
 
     def test_literal_type(self) -> None:
+        a = self.fx.a
         b = self.fx.b  # Reminder: b is a subclass of a
 
         lit1 = self.fx.lit1
@@ -1064,6 +1065,7 @@ def test_literal_type(self) -> None:
         self.assert_same(lit1, lit1)
         self.assert_same(UnionType([lit1, lit2]), UnionType([lit1, lit2]))
         self.assert_same(UnionType([lit1, lit2]), UnionType([lit2, lit1]))
+        self.assert_same(UnionType([a, b]), UnionType([b, a]))
         self.assert_not_same(lit1, b)
         self.assert_not_same(lit1, lit2)
         self.assert_not_same(lit1, lit3)
diff --git a/test-data/unit/check-unions.test b/test-data/unit/check-unions.test
index e8921f30cdcf..08c183cb3ed1 100644
--- a/test-data/unit/check-unions.test
+++ b/test-data/unit/check-unions.test
@@ -1059,3 +1059,100 @@ x: Union[None, Any]
 y: Union[int, None]
 reveal_type(f(x, y)) # N: Revealed type is "Union[None, Any, builtins.int]"
 reveal_type(f(y, x)) # N: Revealed type is "Union[builtins.int, None, Any]"
+
+[case testNestedProtocolUnions]
+from typing import Union, Iterator, Iterable
+def foo(
+    values: Union[
+        Iterator[Union[
+            Iterator[Union[Iterator[int], Iterable[int]]],
+            Iterable[Union[Iterator[int], Iterable[int]]],
+        ]],
+        Iterable[Union[
+            Iterator[Union[Iterator[int], Iterable[int]]],
+            Iterable[Union[Iterator[int], Iterable[int]]],
+        ]],
+    ]
+) -> Iterator[int]:
+    for i in values:
+        for j in i:
+            for k in j:
+                yield k
+foo([[[1]]])
+[builtins fixtures/list.pyi]
+
+[case testNestedProtocolGenericUnions]
+from typing import Union, Iterator, List
+def foo(
+    values: Union[
+        Iterator[Union[
+            Iterator[Union[Iterator[int], List[int]]],
+            List[Union[Iterator[int], List[int]]],
+        ]],
+        List[Union[
+            Iterator[Union[Iterator[int], List[int]]],
+            List[Union[Iterator[int], List[int]]],
+        ]],
+    ]
+) -> Iterator[int]:
+    for i in values:
+        for j in i:
+            for k in j:
+                yield k
+foo([[[1]]])
+[builtins fixtures/list.pyi]
+
+[case testNestedProtocolGenericUnionsDeep]
+from typing import TypeVar, Union, Iterator, List
+T = TypeVar("T")
+Iter = Union[Iterator[T], List[T]]
+def foo(
+    values: Iter[Iter[Iter[Iter[Iter[int]]]]],
+) -> Iterator[int]:
+    for i in values:
+        for j in i:
+            for k in j:
+                for l in k:
+                    for m in l:
+                        yield m
+foo([[[[[1]]]]])
+[builtins fixtures/list.pyi]
+
+[case testNestedInstanceUnsimplifiedUnion]
+from typing import TypeVar, Union, Iterator, List, Any
+T = TypeVar("T")
+
+Iter = Union[Iterator[T], List[T]]
+def foo(
+    values: Iter[Union[Any, Any]],
+) -> Iterator[Any]:
+    for i in values:
+        yield i
+foo([1])
+[builtins fixtures/list.pyi]
+
+[case testNestedInstanceTypeAlias]
+from typing import TypeVar, Union, Iterator, List, Any
+T = TypeVar("T")
+
+Iter = Union[Iterator[T], List[T]]
+def foo(
+    values: Iter["Any"],
+) -> Iterator[Any]:
+    for i in values:
+        yield i
+foo([1])
+[builtins fixtures/list.pyi]
+
+[case testNestedInstanceTypeAliasUnsimplifiedUnion]
+from typing import TypeVar, Union, Iterator, List, Any
+T = TypeVar("T")
+
+Iter = Union[Iterator[T], List[T]]
+def foo(
+    values: Iter["Union[Any, Any]"],
+) -> Iterator[Any]:
+    for i in values:
+        yield i
+foo([1])
+[builtins fixtures/list.pyi]