Background: Anorectal squamous cell carcinomas (SCCs) are rare in the United States with < 10,000 cases annually. Uncommonly, patients present with stage IV disease or recurrence after definitive therapy. Limited options exist for these patients. We queried Roswell Park Cancer Institute (RPCI) patient records to determine systemic treatments utilized and outcomes for these patients. Methods: Patients with anal or rectal SCC between 1/1/99 and 7/1/2014 were identified via the cancer registry. 65 patients were flagged for review. From manual review, 31 patients received treatment at RPCI and were deemed evaluable. Demographic data, histology, staging, treatment history, time receiving any specific therapy and response assessment were abstracted from the records. Results: Of the 31 patients, 45% were male, 55% female. Primary tumors were anorectal (84%) or rectal (16%) in origin. 5(16%) presented with rectal SCC. Sites of metastatic disease were most commonly identified as lymph nodes (48%), liver (35) or lung (16%). At the time of analysis 5 (16%) were alive, with 3 (10%) disease free. Median overall survival (OS) was 44.1 months (95% CI, 28.9 - 62.6). The most commonly utilized chemotherapy regimens were 5-fu/cisplatin (n = 22 patients) and taxol (n = 10). Mean time on therapy was 4 months for 5-fu/platinum doublets (n = 24), 4 months for taxanes/platinum combinations (n = 6), 3.4 months for anti-EGFR containing regimens (n = 7) and 2.43 months for taxane monotherapy (n = 10). The most common reasons for discontinuation of therapy were progressive disease (47%) or patient choice (15%). Conclusions: New therapies are desperately needed for advanced anorectal SCCs. At present, 5-FU/cisplatin is the best endorsed and most frequently utilized regimen. Consistent with other reports, platinum doublets and anti-EGFR targeted therapies appear to confer significant benefits, within the realm of 5-fu/cisplatin, with single agent taxanes appearing to have lesser activity. Small absolute patient numbers and lack of reliable response measurements preclude firm conclusions. Future clinical trials to evaluate systemic therapies in advanced anorectal SCCs, including anti-EGFR regimens, are warranted.