We have reported that a novel tumor-associated antigen (Ag), 22-1-1, was expressed in cancer cells derived mainly from the uterus and ovary [K. Sonoda et al., Cancer (Phila.), 77: 1501-1509, 1996]. The 22-1-1 Ag existed not only in adenocarcinomas but also in squamous cell carcinomas in the uterine cervix. Here, a relationship between tumor progression and invasion and 22-1-1 Ag expression was investigated in squamous cell neoplasms of the uterine cervix using immunohistochemical staining. The 22-1-1 Ag was not detected in normal uterine cervix (0 of 10 total cases) and dysplasias (0 of 47 total cases). However, 20% of carcinoma in situ (4 of 20 total cases) and 16.7% of microinvasive carcinomas (2 of 12 total cases) stained positively for 22-1-1 Ag. Moreover, areas depicting microinvasion on histology in uterine cancers (stage Ia) were more strongly stained than carcinoma in situ lesions. 22-1-1 Ag expression was found to be more frequent in invasive squamous cell carcinomas (82.6%; 57 of 69 total cases). The 22-1-1 Ag existed both in the cytoplasm and on the membrane of cancer cells. These findings suggest that 22-1-1 Ag expression might be related to tumor cell progression and invasion in the uterine cervical squamous cell epithelium.