diff --git a/CHANGELOG.md b/CHANGELOG.md
index b706156bc4b3..5a125dcf0f58 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -5,6 +5,7 @@
 ### Fixes
 
 - `[jest-runtime]` Ensure absolute paths can be resolved within test modules ([11943](https://github.com/facebook/jest/pull/11943))
+- `[jest-runtime]` Use typeof type guard instead of instanceof to differentiate ModernFakeTimers and LegacyFakeTimers methods ([#11946](https://github.com/facebook/jest/pull/11946))
 
 ### Chore & Maintenance
 
diff --git a/packages/jest-runtime/src/index.ts b/packages/jest-runtime/src/index.ts
index c8cfa5c17246..b55ec85b4e77 100644
--- a/packages/jest-runtime/src/index.ts
+++ b/packages/jest-runtime/src/index.ts
@@ -30,7 +30,7 @@ import type {
   Module,
   ModuleWrapper,
 } from '@jest/environment';
-import {LegacyFakeTimers, ModernFakeTimers} from '@jest/fake-timers';
+import type {LegacyFakeTimers, ModernFakeTimers} from '@jest/fake-timers';
 import type * as JestGlobals from '@jest/globals';
 import type {SourceMapRegistry} from '@jest/source-map';
 import type {RuntimeTransformResult, V8CoverageResult} from '@jest/test-result';
@@ -1963,7 +1963,7 @@ export default class Runtime {
       getRealSystemTime: () => {
         const fakeTimers = _getFakeTimers();
 
-        if (fakeTimers instanceof ModernFakeTimers) {
+        if (this._areModernFakeTimers(fakeTimers)) {
           return fakeTimers.getRealSystemTime();
         } else {
           throw new TypeError(
@@ -1984,7 +1984,7 @@ export default class Runtime {
       runAllImmediates: () => {
         const fakeTimers = _getFakeTimers();
 
-        if (fakeTimers instanceof LegacyFakeTimers) {
+        if (!this._areModernFakeTimers(fakeTimers)) {
           fakeTimers.runAllImmediates();
         } else {
           throw new TypeError(
@@ -2000,7 +2000,7 @@ export default class Runtime {
       setSystemTime: (now?: number | Date) => {
         const fakeTimers = _getFakeTimers();
 
-        if (fakeTimers instanceof ModernFakeTimers) {
+        if (this._areModernFakeTimers(fakeTimers)) {
           fakeTimers.setSystemTime(now);
         } else {
           throw new TypeError(
@@ -2018,6 +2018,12 @@ export default class Runtime {
     return jestObject;
   }
 
+  private _areModernFakeTimers(
+    fakeTimers: ModernFakeTimers | LegacyFakeTimers<unknown>,
+  ): fakeTimers is ModernFakeTimers {
+    return typeof (fakeTimers as ModernFakeTimers).setSystemTime === 'function';
+  }
+
   private _logFormattedReferenceError(errorMessage: string) {
     const testPath = this._testPath
       ? ` From ${slash(path.relative(this._config.rootDir, this._testPath))}.`