The association of cyclophosphamide therapy with the development of urothelial malignancy has been documented. Bladder diverticula associated with squamous cell carcinoma were also identified. In addition, incorporation of human papillomavirus (HPV) deoxyribonucleic acid (DNA) has been previously shown in urothelial carcinoma by in situ hybridization technique. Here a case is reported of bladder squamous cell carcinoma occurring four years after intravenous pulse therapy with cyclophosphamide in a patient with bladder diverticula where HPV was identified in the lesion. To present knowledge, this is the first case report of bladder squamous cell carcinoma with simultaneous occurrence of three risk factors for urothelial malignancy: cyclophosphamide therapy, diverticulum, and HPV infection.