Colorectal cancer is one of the leading causes of cancer-related death worldwide. Molecular biomarkers could help to predict patient outcome and to identify patients who benefit from adjuvant therapy. Pontin and Reptin are ATPases which are involved in transcriptional regulation, DNA damage repair and regulation of cell proliferation. Many interaction partners of Pontin and Reptin such as β-catenin and c-myc are important factors in carcinogenesis. We hypothesized that Pontin and Reptin expression may be a negative predictor for survival in colorectal carcinoma. Specimens from 115 patients with primary colon adenocarcinomas UICC stage III and primary rectal adenocarcinomas UICC stage II and III curatively resected at the Department of Surgery, Charité Berlin, were evaluated. Clinical follow-up data were complete and mean follow-up time of patients was 51.8 months. We evaluated the expression of Pontin, Reptin and Ki-67 by immunohistochemistry. Patients with Pontin-positive carcinomas showed no differences in recurrence-free survival (p=0.109) and overall survival (p=0.197). There were no differences in Reptin-positive carcinomas and Ki-67-positive carcinomas in recurrence-free survival (p=0.443 and p=0.160) and overall survival (p=0.477 and p=0.687). Patients with Pontin-positive colorectal carcinomas receiving adjuvant therapy had a significantly worse recurrence-free survival (p=0.008) and overall survival (p=0.011) than Pontin-negative patients with adjuvant therapy. In UICC stage III, Pontin-positive colorectal carcinomas had a significantly worse recurrence-free survival (p=0.028). Pontin-positivity seems to be a negative predictor for response to adjuvant therapy in colorectal cancer patients and may help to identify patients with adverse outcome in advanced tumor stages.