diff --git a/mypy/checker.py b/mypy/checker.py
index 4f06df731d05..e55608ab896a 100644
--- a/mypy/checker.py
+++ b/mypy/checker.py
@@ -5363,6 +5363,12 @@ def flatten_types(t: Type) -> List[Type]:
 
 def get_isinstance_type(expr: Expression,
                         type_map: Dict[Expression, Type]) -> Optional[List[TypeRange]]:
+    if isinstance(expr, OpExpr) and expr.op == '|':
+        left = get_isinstance_type(expr.left, type_map)
+        right = get_isinstance_type(expr.right, type_map)
+        if left is None or right is None:
+            return None
+        return left + right
     all_types = get_proper_types(flatten_types(type_map[expr]))
     types: List[TypeRange] = []
     for typ in all_types:
diff --git a/test-data/unit/check-union-or-syntax.test b/test-data/unit/check-union-or-syntax.test
index 7137fcbfe310..3e5a19b8fe61 100644
--- a/test-data/unit/check-union-or-syntax.test
+++ b/test-data/unit/check-union-or-syntax.test
@@ -169,3 +169,30 @@ y: B
 class C(list[int | None]):
     pass
 [builtins fixtures/list.pyi]
+
+[case testUnionOrSyntaxInIsinstance]
+# flags: --python-version 3.10
+class C: pass
+
+def f(x: int | str | C) -> None:
+    if isinstance(x, int | str):
+        reveal_type(x)  # N: Revealed type is "Union[builtins.int, builtins.str]"
+    else:
+        reveal_type(x)  # N: Revealed type is "__main__.C"
+
+def g(x: int | str | tuple[int, str] | C) -> None:
+    if isinstance(x, int | str | tuple):
+        reveal_type(x)  # N: Revealed type is "Union[builtins.int, builtins.str, Tuple[builtins.int, builtins.str]]"
+    else:
+        reveal_type(x)  # N: Revealed type is "__main__.C"
+[builtins fixtures/isinstance_python3_10.pyi]
+
+[case testUnionOrSyntaxInIsinstanceNotSupported]
+# flags: --python-version 3.9
+from typing import Union
+def f(x: Union[int, str, None]) -> None:
+    if isinstance(x, int | str): # E: Unsupported left operand type for | ("Type[int]")
+        reveal_type(x)  # N: Revealed type is "Union[builtins.int, builtins.str]"
+    else:
+        reveal_type(x)  # N: Revealed type is "None"
+[builtins fixtures/isinstance.pyi]
diff --git a/test-data/unit/fixtures/isinstance_python3_10.pyi b/test-data/unit/fixtures/isinstance_python3_10.pyi
new file mode 100644
index 000000000000..abb37ea81c00
--- /dev/null
+++ b/test-data/unit/fixtures/isinstance_python3_10.pyi
@@ -0,0 +1,29 @@
+# For Python 3.10+ only
+from typing import Tuple, TypeVar, Generic, Union, cast, Any, Type
+import types
+
+T = TypeVar('T')
+
+class object:
+    def __init__(self) -> None: pass
+
+class type(Generic[T]):
+    def __init__(self, x) -> None: pass
+    def __or__(self, x) -> types.Union: pass
+
+class tuple(Generic[T]): pass
+
+class function: pass
+
+def isinstance(x: object, t: Union[Type[object], Tuple[Type[object], ...], types.Union]) -> bool: pass
+def issubclass(x: object, t: Union[Type[object], Tuple[Type[object], ...]]) -> bool: pass
+
+class int:
+    def __add__(self, other: 'int') -> 'int': pass
+class float: pass
+class bool(int): pass
+class str:
+    def __add__(self, other: 'str') -> 'str': pass
+class ellipsis: pass
+
+NotImplemented = cast(Any, None)
diff --git a/test-data/unit/lib-stub/types.pyi b/test-data/unit/lib-stub/types.pyi
index 02113aea3834..6fc596ecbf13 100644
--- a/test-data/unit/lib-stub/types.pyi
+++ b/test-data/unit/lib-stub/types.pyi
@@ -1,4 +1,5 @@
 from typing import TypeVar
+import sys
 
 _T = TypeVar('_T')
 
@@ -8,3 +9,7 @@ class bool: ...
 
 class ModuleType:
     __file__ = ... # type: str
+
+if sys.version_info >= (3, 10):
+    class Union:
+        def __or__(self, x) -> Union: ...