Sarcoidosis is a multisystem granulomatous disorder characterized by helper T cell inflammation. Sarcoid-like reaction (SLR) is a well-defined entity and may be related with several malignant disorders and/or their therapies. SLR has been reported more than 20 years ago and in recent years in cases treated by checkpoint inhibitors (CPIs). Better outcome has been reported in cases developing granulomatous reaction and/or SLRs during CPI treatments. However, these lesions clinically may be thought as disease progression and may cause to stop treatment or alterations. These therapeutic manipulations may be harmful for the patients. Clinicians should be aware of SLRs in cases treated by CPIs and tissues must be sampled and reviewed by an experienced pathologist to avoid misdiagnosis and also unnecessary CPI treatment cessations.Significance StatementClinicians should be aware of sarcoid-like reactions in cases treated by checkpoint inhibitors and tissues must be sampled and reviewed by an experienced pathologist to avoid misdiagnosis and CPI treatment stops.