Intravesical instillation of bacillus Calmette-Guerin (BCG) after transurethral cancer resection is an approved part of the management of non-muscle invasive bladder cancer (NMIBC). The onset of polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) following this immunotherapy is anecdotal. We report the case of a 69-year-old male patient suffering from boxing-glove swelling of the hand associated with bilateral pain, aching and stiffness in the shoulders and pelvic girdles, which occurred after a cycle of six intravesical instillations of BCG. Polymyalgia rheumatica associated with RS3PE was diagnosed, prednisone therapy started and definitively stopped after 13 months. During a 16-year follow-up, no alternative diagnosis was possible. The role of genetic factors and of the senescence of the immune system is discussed. According to our best knowledge, this is the first case report of PMR associated with RS3PE following intravesical instillation of BCG.