INTRODUCTION: Squamous cell carcinoma of the gastrointestinal (GI) tract is a rare malignancy. When encountered, it usually involves the esophagus or the anal canal. Squamous cell carcinoma of the rectum is extremely unusual and unlike squamous cell carcinoma of the esophagus and anal canal, little is known about the etiology, prognosis, and optimal treatment. We report an unusual case of rectal squamous cell carcinoma in a patient with hematochezia and constipation. CASE DESCRIPTION/METHODS: A seventy-six-year-old female with a past surgical history of TAH-BSO was initially referred from her OB/GYN who noted a heterogeneous, solid and cystic mass measuring 9.3 × 10.5 × 9.3 cm in the deep pelvis on computer tomography (CT) scan. The patient reported symptoms of intermittent lower gastrointestinal bleeding, decreased appetite, and right upper quadrant pain. She also complained of occasional constipation and a change in the texture and consistency of her stool. She denied NSAID use, dysphagia, odynophagia, nausea, vomiting, hematemesis, diarrhea, or unintentional weight loss. A palpable 1 cm ulcerated rectal mass was noted on digital rectal exam. The pelvic exam was notable for a large palpable mass appreciated in pelvis abutting posterior vaginal wall A diagnostic colonoscopy was performed which showed a 5 mm polyp in the cecum, a 1–2 cm subepithelial lesion seen in the mid rectum anda single 1 cm ulcerated lesion in the rectum which was biopsied with cold forceps. Non-bleeding internal hemorrhoids were also identified. Surgical pathology showed that the tumor cells were positive for p63, CK 5/6, CAM 5.2, KI-67 (95%), CK 7, p40 & p16 and negative for CD 56, synaptophysin, Chromogranin, CDX-2 and CK 20. The immunohistochemistry results supported the diagnosis of poorly differentiated squamous cell carcinoma. Endoscopic ultrasound (EUS) was performed for further evaluation of the pelvic mass. A 71.3 mm × 43.0 mm peri-rectal mass with solid and cystic components was visualized. Two sub centimeter lymph nodes were visualized and measured in the perirectal region. Fine needle biopsy wasperformed of the perirectal mass and surgical pathology and cytology were consistent with poorly differentiated squamous cell carcinoma. FNB of the lymph nodes were not performed due to the small size of the lymph nodes. DISCUSSION: Squamous cell carcinoma of the rectum is a rare clinical entity. Clinicians should be aware of SCC as a differential in evaluating hematochezia and rectal masses.Figure 1.: Colonoscopy showing rectal mass.Figure 2.: Endoscopic ultrasound of rectal mass.