BACKGROUND: The etiology and significance of port site recurrence occurring after laparoscopic-assisted resection for colorectal cancers will not be determined until controlled clinical trials determine if it is a predictor of outcome. Indirect evidence in support of transcoelomic spread of viable cancer cells to port sites during resection can be postulated by the presence of free cells on the fresh surface of colorectal specimens during primary resection. PURPOSE: The study contained herein was undertaken to determine the incidence of free surface colorectal cancer cells by cytology during elective open resection and to correlate their presence with clinicopathologic variables. METHODS: Fresh clamped and ligated consecutive colorectal cancer specimens were assessed in the operating room during primary resection for the presence of free colorectal cancer cells during an 18 month period at one institution. Clinicopathologic variables were assessed prospectively and blinded to cytology results. Interobserver reliability of cytologists was excellent (unweighted kappa, 0.93). RESULTS: Overall, 15 of 103 (14.6 percent) colorectal cancers had positive cytology for cancer cells on the peritoneal or perirectal surface of the bowel. TS and T4 tumors, the size or site of the tumor, lymph node status, mucinous characteristic. degree of differentiation, and the presence of vascular or neural invasion did not reach statistical significance as predictors of positive cytology in this study sample. The operative procedure performed was a statistically significant predictor of positive cytology. More than 50 percent of lymph nodes involved (28 percent), poorly differentiated tumors (28 percent), and the presence of liver metastases (22 percent) demonstrated a higher incidence of positive cytology, but this did not reach significant levels because of the limited power of the study sample for subgroup analysis. DISCUSSION: The presence of free surface colorectal cancer cells gives only indirect support to the transcoelomic route to port site recurrence. The significance and true incidence will only be determined by prospective database analysis and randomized, controlled trials.