We have previously shown that human colorectal carcinoma cell lines, RCM‐1 and CoCM‐1, synthesize alpha‐1‐antitrypsin (α1‐AT) in culture. We have studied immunohistochemically the incidence of α1‐AT on histologic sections from paraffin‐embedded tissues of surgically resected colorectal carcinomas and their metastatic foci, polypectomized adenomas, and normal mucosae. α1‐AT was detected in 89 (61%) of 145 carcinomas (including 14 carcinomas in adenoma), and 12 (39%) of 31 adenomas. But only 2 (4%) of 55 normal colorectal mucosae were positive for α1‐AT. In metastatic tumor cells of colorectal carcinomas in lymph nodes and other organs, α1‐AT positivity was 60% and 82%, respectively. The incidence of α1‐AT was markedly higher in advanced adenocarcinomas than in early ones and more frequent in adenocarcinomas of right side (including transverse colon) than those of left side and rectum, regardless of their histological malignancy grades. In mucinous carcinomas the frequency was greater (8 of 9 cases) than in conventional adenocarcinomas. Clinical follow‐up of the patients with colorectal carcinomas suggested that α1‐AT positivity in Dukes' stage A/B tends to correlate with unfavorable prognosis irrespective of the grade of histologic differentiation of carcinoma, but there is no significant relation in Dukes' stage C/D. Our findings suggest that α1‐AT in colorectal carcinoma is related to the invasive and metastatic capacity. It may thus serve as a biologic marker for prognosis of colorectal carcinomas at relatively early stages (Dukes' stage A/B). Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company