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Many studies that have calculated prostate cancer volumes from microscopic slides have used correction factors, ranging from 1.22 to 1.5, to compensate for tissue shrinkage during tissue processing. We undertook a study to measure tissue shrinkage directly because our experience suggested less shrinkage than that reported by others. Ten prostatectomy specimens were processed in a uniform manner. Multiple identical linear measurements were taken at four stages of processing: in the fresh state, following fixation, following processing, and from the microscopic slide. Linear shrinkage following fixation was minimal (4.1%) but increased to 14.5% following tissue processing. With rehydration and expansion on the flotation bath, tissues swelled so that net linear tissue shrinkage was 4.3%, and net volumetric tissue shrinkage was 12.4%, which translates into a correction factor for tissue shrinkage of 1.14. The following variables had no statistically significant effect on shrinkage: concentration of formalin, whole-mount versus quadrant section, thickness of tissue slices, length of time in the alcohol dehydration steps, and temperature of the flotation bath over a range of 35 to 45°C. This study suggests that (a) tissue-shrinkage correction factors that have been used in some previous studies may not be applicable for all laboratories because of interlaboratory variations in tissue-processing procedures or differences in measuring shrinkage; and (b) some calculated tumor volumes that have been used for prognostic thresholds may be high because of inflated tissue-shrinkage correction factors.