OBJECTIVE: To develop a distance measure based methodology to support the morphological evaluation of high grade prostatic intraepithelial neoplasia (PIN), a direct precursor of prostate cancer. METHODS: Eight morphological and cellular features were analysed in 20 cases of high grade PIN found in radical prostatectomy specimens from patients with adenocarcinoma. The diagnostic distance was evaluated to measure the extent to which the feature outcomes of the individual high grade PIN cases differed from the expected outcome profile of normal prostate, low and high grade PIN, and cribriform and large acinar adenocarcinoma. The belief value for high grade PIN was evaluated with a Bayesian belief network (BBN). RESULTS: Complete separation existed between the cumulative absolute diagnostic distances of these 20 cases from the prototype feature outcomes of high grade PIN and normal prostate the values for which were < or = 3 (range 0 to 3) and > or = 9 (range 9 to 15), respectively. The distances from low grade PIN (range 3 to 9), cribriform adenocarcinoma (range 2 to 8), and large acinar adenocarcinoma (range 5 to 10) were intermediate and showed overlap in their distribution. When taking into consideration whether the severity of feature changes was increasing or decreasing in comparison with the category prototype outcomes, the cumulative directional diagnostic distances from high grade PIN ranged from -3 to +3. Positive distance values were seen relative to low grade PIN (range +3 to +9) and relative to normal prostate (range +9 to +15). Negative values were found relative to cribriform adenocarcinoma (range -8 to +2). The distance values from large acinar adenocarcinoma ranged from -2 to +4 and partly overlapped with those from the high grade PIN category. A bivariate scattergram derived from both diagnostic distance measures showed excellent separation between the groups' distances. BBN analysis confirmed the morphology based diagnosis. The distance evaluation resulted in 18 cases whose belief value for high grade PIN ranged from 0.60 to 0.87. In the remaining two cases the results of the BBN analysis showed a belief value of 0.50 and 0.57 for low grade PIN and of 0.49 and 0.38 for high grade PIN, respectively. CONCLUSIONS: Distance measure based methodology represents a useful diagnostic decision support tool for the accurate evaluation of high grade PIN.