A new in vitro method for early detection of prostatic cancer is described. The results of tissue culture of prostatic epithelial cells harvested during digital rectal examination were compared with patient-matched biopsy findings in a double-blind study. An arbitrary combination of five culture parameters (displayed in vitro by cultured prostatic cells and related to neoplastic and differentiation features of the sample [growth capacity, proportion of epithelium and morphologic atypia of overlapping cells, multinucleated cells and vacuolized cells]), was created after two weeks of culture; this combination, referred to as the Global Tissue Culture Score (GTCS), ranged from 0 (negative result or benign behavior) to 15 (highly abnormal neoplastic behavior). The GTCS was significantly higher in biopsy-proven prostatic carcinoma than in other prostatic diseases. The combination of GTCS and patient age was highly sensitive and specific for a diagnosis of prostatic carcinoma, according to the biopsy results. Our findings indicate that the early diagnosis of prostatic carcinoma can be obtained by a tissue culture method which allows in vitro growth of epithelial cells harvested through digital rectal prostatic massage. This method is easy to perform, is non-invasive, is able to discriminate between biologically aggressive and non-aggressive neoplasms, and may be useful for mass screening of prostatic carcinoma in conjunction with digital rectal exam. Early diagnosis of prostatic carcinoma may maximize the potential curative value of radical prostatectomy or other forms of therapy for this highly prevalent cancer.