The sarcoid-like reaction represents an autoinflammatory cause of mediastinal and hilar lymphadenopathy but may also involve other lymph node regions and organs. This rare phenomenon has mainly been reported in patients with Hodgkin’s lymphoma (HL) or solid tumors (particularly melanoma) undergoing immunotherapy and chemotherapy. Cases in non-Hodgkin’s lymphoma (NHL) are very uncommon. We present an uncommon case of a patient with primarily mediastinal diffuse large B-cell lymphoma (DLBCL) who showed a CT-based partial response in interim staging, whereas at end-of-treatment multiple newly enlarged and hypermetabolic mediastinal and bilateral hilar lymph nodes were detected by 18F-FDG PET/CT imaging. A subsequent histological workup determined a sarcoid-like reaction without any lymphomatous tissue. Therefore, sarcoid-like reactions should be considered as a potential pitfall in Deauville staging with 18F-FDG PET/CT imaging for patients with NHL.