Recent advances in molecular techniques have given the opportunity to assess genomic and proteomic alterations comprehensively and rapidly in routinely acquired tissue samples. In particular, new markers derived from qualitative and quantitative DNA, RNA, and protein analysis have provided additional objective information to supplant and extend the morphologic interpretations and have been increasingly integrated into the final surgical pathology diagnosis. In this review several recently developed molecular techniques are described and illustrated. The focus is on prostate cancer diagnostics, as an example of their application.