diff --git a/mypy/checker.py b/mypy/checker.py
index 307afe8568d5..f31d4c300e19 100644
--- a/mypy/checker.py
+++ b/mypy/checker.py
@@ -2693,12 +2693,7 @@ def flatten(t: Expression) -> List[Expression]:
 
 
 def get_isinstance_type(expr: Expression, type_map: Dict[Expression, Type]) -> Type:
-    type = type_map[expr]
-
-    if isinstance(type, TupleType):
-        all_types = type.items
-    else:
-        all_types = [type]
+    all_types = [type_map[e] for e in flatten(expr)]
 
     types = []  # type: List[Type]
 
diff --git a/test-data/unit/check-isinstance.test b/test-data/unit/check-isinstance.test
index 9a1b787391a9..43dbfd8321d1 100644
--- a/test-data/unit/check-isinstance.test
+++ b/test-data/unit/check-isinstance.test
@@ -31,6 +31,22 @@ z = [a.y for b in y for a in b]
 
 [builtins fixtures/list.pyi]
 
+[case testIsinstanceNestedTuple]
+from typing import Union, List, Tuple, Dict
+def f(x: Union[int, str, List]) -> None:
+    if isinstance(x, (str, (int,))):
+        reveal_type(x)  # E: Revealed type is 'Union[builtins.int, builtins.str]'
+        x[1]  # E: Value of type "Union[int, str]" is not indexable
+    else:
+        reveal_type(x)  # E: Revealed type is 'builtins.list[Any]'
+        x[1]
+    reveal_type(x)  # E: Revealed type is 'Union[builtins.int, builtins.str, builtins.list[Any]]'
+    if isinstance(x, (str, (list,))):
+        reveal_type(x)  # E: Revealed type is 'Union[builtins.str, builtins.list[Any]]'
+        x[1]
+    reveal_type(x)  # E: Revealed type is 'Union[builtins.int, builtins.str, builtins.list[Any]]'
+[builtins fixtures/isinstancelist.pyi]
+
 [case testClassAttributeInitialization-skip]
 class A:
     x = None # type: int
diff --git a/test-data/unit/fixtures/isinstancelist.pyi b/test-data/unit/fixtures/isinstancelist.pyi
index 4b3569875ab9..9096961b06ab 100644
--- a/test-data/unit/fixtures/isinstancelist.pyi
+++ b/test-data/unit/fixtures/isinstancelist.pyi
@@ -1,4 +1,4 @@
-from typing import builtinclass, Iterable, Iterator, Generic, TypeVar, List, Mapping, overload, Tuple
+from typing import builtinclass, Iterable, Iterator, TypeVar, List, Mapping, overload, Tuple, Set, Union
 
 @builtinclass
 class object:
@@ -11,7 +11,7 @@ class type:
 class tuple: pass
 class function: pass
 
-def isinstance(x: object, t: type) -> bool: pass
+def isinstance(x: object, t: Union[type, Tuple]) -> bool: pass
 
 @builtinclass
 class int:
@@ -27,14 +27,14 @@ T = TypeVar('T')
 KT = TypeVar('KT')
 VT = TypeVar('VT')
 
-class list(Iterable[T], Generic[T]):
+class list(Iterable[T]):
     def __iter__(self) -> Iterator[T]: pass
     def __mul__(self, x: int) -> list[T]: pass
     def __setitem__(self, x: int, v: T) -> None: pass
     def __getitem__(self, x: int) -> T: pass
     def __add__(self, x: List[T]) -> T: pass
 
-class dict(Iterable[KT], Mapping[KT, VT], Generic[KT, VT]):
+class dict(Iterable[KT], Mapping[KT, VT]):
     @overload
     def __init__(self, **kwargs: VT) -> None: pass
     @overload
@@ -42,3 +42,9 @@ class dict(Iterable[KT], Mapping[KT, VT], Generic[KT, VT]):
     def __setitem__(self, k: KT, v: VT) -> None: pass
     def __iter__(self) -> Iterator[KT]: pass
     def update(self, a: Mapping[KT, VT]) -> None: pass
+
+class set(Iterable[T]):
+    def __iter__(self) -> Iterator[T]: pass
+    def add(self, x: T) -> None: pass
+    def discard(self, x: T) -> None: pass
+    def update(self, x: Set[T]) -> None: pass