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Prostate cancer surgery risks erectile problems and incontinence for the patient. An instrument for guiding surgeons to avoid nerve bundle damage and ensure complete cancer removal is desirable. We present a tactile resonance sensor made of PZT ceramics, mounted in a 3D motorized translation stage for scanning and measuring tissue stiffness for detecting cancer in human prostate. The sensor may be used during surgery for guidance, scanning the prostate surface for the presence of cancer, indicating migration of cancer cells into surrounding tissue. Ten fresh prostates, obtained from patients undergoing prostate cancer surgery, were cut into 0.5 cm thick slices. Each slice was measured for tissue stiffness at about 25 different sites and compared to histology for validation cancer prediction by stiffness. The statistical analysis was based on a total of 148 sites with non-cancer and 40 sites with cancer. Using a generalized linear mixed model (GLMM), the stiffness data predicted cancer with an area under the curve of 0.74, after correcting for overfitting using bootstrap validation. Mean prostate stiffness on the logarithmic scale (p = 0.015) and standardized Z-scores (p = 0.025) were both significant predictors of cancer. This study concludes that stiffness measured by the tactile resonance sensor is a significant predictor of prostate cancer with potential for future development towards a clinical instrument for surgical guidance.