This case describes a rare presentation of a diffuse large B-cell lymphoma not otherwise specified (DLBC NOS) in the gallbladder. We report the case of an 89-year-old male who initially presented with a two-week history of weakness and abdominal discomfort. We performed laparoscopic cholecystectomy for suspicion of acute cholecystitis. After the initial uneventful course, readmission occurred for persisting weakness a few weeks after surgery. Computed tomography revealed progressive retroperitoneal lymphadenopathy. With new emerging neurological symptoms, taking into account the histopathological findings of the gallbladder specimen, the diagnosis of DLBCL NOS was confirmed. Due to the rapid clinical deterioration and extranodal involvement, the patient opted against further therapy. When the suspicion of cholecystitis is inconclusive, rare differential diagnoses need to be considered. This analysis may improve the understanding of the presentation and course of DLBC NOS in abdominal organs and could form the basis for a systematic review to improve diagnosis and therapy.