Cancer involvement of the colonic serosa is designated pT4a by the American Joint Committee on Cancer Staging Manual, 7th edition. The manual defines criteria for pT4a as either tumor penetration of the serosa or comingling of cancer cells and mesothelial cells in histologic sections. Unfortunately, the pT4a grouping is inconsistently applied, because these guidelines are overly limited: fibroinflammatory changes near the serosa may be associated with peritoneal metastases even in the absence of overt peritoneal penetration. Thus, reliable ancillary techniques for detecting serosal penetration by the tumor and accurate criteria for stage assessment are needed. We evaluated the utility of cytologic preparations in determining tumor stage by comparing results of serosal scrape cytology with histologic stage assessment of 120 colon cancer resection specimens. We correlated our findings with the presence and type of inflammatory changes near the serosa to determine which, if any, are reliable indicators of peritoneal penetration. Cytologic smears from all pT1 and pT2 tumors were negative for carcinoma. However, 13 (19%) pT3 tumors showed cancer in cytologic smears, all of which were deeply invasive. In fact, 46% of pT3 cancers present ≤1 mm from a serosal tissue reaction were associated with cancer in cytologic preparations from the serosa, which was comparable to pT4a tumors (55%). We conclude that cytologic smears improve detection of peritoneal penetration among pT3 tumors compared with histology alone. Tumors close (≤1 mm) to a fibroinflammatory tissue reaction on the serosa are likely associated with peritoneal involvement by cancer. Peritumoral abscesses that communicate with the serosa and hemorrhage or fibrin on the serosa also predict cancer involvement of the peritoneum. The presence of these findings among deeply invasive cancers should prompt their classification as pT4a lesions.