This study aimed to identify potential abnormalities of retinoblastoma protein (pRb) and p16(INK4a) (p16) expression in resectable colorectal carcinomas (CRCs) and to assess the prognostic significance of pRb and p16 levels in patients with CRC. From July 1990 through December 1993, 117 consecutive patients with CRC underwent curative resection with radical lymphadenectomy. The resected specimens were examined immunohistochemically using monoclonal antibodies to identify abnormalities of pRb and p16 expression. The association of pRb and p16 expression status with clinicopathologic features was analyzed retrospectively. The Cox proportional hazards model was used to identify factors independently affecting survival after resection. The median follow-up period was 62 months. Aberrant expression of pRb and p16 was identified in 82 (70%) and 87 (74%) patients, respectively. Coincident abnormalities of these proteins occurred in 61 (52%) patients. Loss of pRb expression correlated with tumor site (P = 0.0119), whereas p16 overexpression correlated with tumor size (P = 0.0034). Coincident abnormalities of pRb and p16 were associated with TNM tumor stage (P = 0.011). The outcome after resection was worse in patients with aberrant expression of pRb and/or p16 than in patients with normally expressed pRb and p16 (for pRb, P = 0.0151; for p16, P = 0.0247). Coincident abnormalities of pRb and p16 indicated the worst patient survival (P = 0.0310). Aberrant expression of pRb and p16 independently affected postresection survival (relative risk = 6.312, P <0.0001; relative risk = 5.994, P <0.0001, respectively). Most CRCs demonstrate aberrant expression of pRb and/or p16 at resectable stages. Aberrant expression of pRb and p16, alone and in combination, heralds poor prognosis in patients with CRC.