Rationale: Colorectal cancer is one of the most commonly diagnosed cancers worldwide, and the majority arise from neoplastic adenomatous polyps. Bladder involvement in colorectal cancer is uncommon and found in approximately 3% of the cases, most commonly in sigmoid and rectal tumors and the diagnosis is classically based on biopsies of affected tissues. Patient concerns: A 68-year-old male with no significant past medical history underwent diagnostic colonoscopy for abdominal distension and constipation with positive fecal occult blood test ordered by the primary care physician. Diagnosis: Colonoscopy showed a sigmoid mass with biopsy finding of tubulovillous adenoma. Laparoscopy was performed for sigmoid colonic resection, but as the mass was large, a diverting loop colostomy and multiple biopsies were performed revealing tubulovillous adenoma again. Postoperative workup revealed right hydronephrosis, and cystoscopy was performed confirming bladder wall invasion with biopsies showing benign bladder wall tissue with no evidence of dysplasia or malignancy. Furthermore, computed tomography (CT)-guided core-needle biopsies of the colonic mass were performed but revealed adenomatous colonic mucosa without evidence of carcinoma. Intervention: Definitive surgical en bloc excision of the tumor and anterior bladder wall was performed with urology team until grossly free margins were attained. Final pathology revealed well-differentiated mucinous adenocarcinoma arising from a preexisting tubulovillous adenoma with direct invasion of the bladder wall. Outcomes: The patient's postoperative recovery was uneventful, and he was discharged 2 weeks postoperatively with planned adjuvant chemotherapy. Lessons: This case represents a classical presentation of invasive colorectal cancer. Perioperative workup, however, was confounded by failure of open, cystoscopic, and CT-guided biopsies to establish a tissue diagnosis for directed therapy. Upon literature review, evidence exists to support our approach to this unique dilemma.