Isoantigens A, B, and H, present in epithelial cells of some normal tissues, could not be detected when carcinoma developed in these tissues. The specific red cell adherence test (SRCA), a modification of Coombs’ mixed cell agglutination test, was used for their detection. The test is highly sensitive and specific. The age of the paraffin-embedded tissues and hematoxylin-and-eosin stained slides did not affect the sensitivity and specificity of the test. The loss of the antigens was increasingly progressive from carcinoma in situ to anaplastic, invasive, and metastatic carcinoma, and is interpreted as evidence of immunologic dedifferentiation analogous to morphologic dedifferentiation of anaplasia. Three hundred and fifty-five primary carcinomas of the uterine cervix, lung, pancreas, and stomach, and 578 metastatic carcinomas of these organs were studied. With few exceptions, the loss of the isoantigens preceded the formation of distant metastases. The test holds promise (1) to be valuable in the diagnosis of early carcinoma in tissues that normally contain the three antigens and in the prognosis of advanced carcinoma; and (2) to reduce the need for radical surgery in carcinoma in situ of the cervix.