Prostatic intra-epithelial neoplasia (PIN, or intraductal dysplasia) is considered a precursor of invasive carcinoma, characterized by proliferation and anaplasia of cells lining prostatic ducts and acini. The highest grade of PIN, Grade 3, is thought to represent carcinoma in situ. To quantitate the degree of disruption of the basal cell layer in human prostatic ducts and acini as a potential marker of early invasion in PIN, a monoclonal antibody to keratin proteins of 49, 51, 57, and 66 kd which selectively labels the prostatic basal cell layer was used. A total of 1093 acini with PIN were identified in 14 cases with invasive carcinoma. Tumor cells consistently failed to be decorated with this antibody. The frequency of disruption of the basal cell layer increased with increasing grades of PIN, with disruption present in 0.7% of cases of PIN 1, 15% of cases of PIN 2, and 56% of cases of PIN 3. The amount of disruption of the basal cell layer also increased with increasing grades of PIN, with loss of more than one third of the basal layer in 52% of foci of PIN 3 compared with less than 2% in lower grades of PIN. Disruption of the basal layer was more common in acini adjacent to invasive carcinoma than in distant acini. These findings suggest that early invasion in prostate cancer is characterized by disruption of the basal layer, and that invasion occurs commonly in association with foci of high-grade prostatic intra-epithelial neoplasia.