Prostate epithelial differentiation is dictated by its surrounding stroma which determines androgen induced growth responsiveness and expression of specific secretory proteins in normal prostate gland. During neoplastic progression, organ specific stroma has been shown to determine the rate of neoplastic progression from androgen-dependent to androgen-independent and metastatic states. Although growth factors and extracellular matrix are recognized as important contributors to prostate epithelial growth, hormonal responsiveness, and neoplastic progression, the exact mechanism of intercellular communication between stromal and epithelial cells remains undefined. In addition to the importance of defining the reciprocal interaction between stromal and epithelial interaction in the prostate, clonal interaction between two dissimilar prostate epithelial cell is also recognized to contribute to disease progression. In this review, we summarized recent advances made in delineating molecular mechanisms underlying stromal epithelial interaction and clonal interaction between androgen-dependent and androgen-independent prostate cancer cells in vivo and in culture. Understanding cellular interaction between prostate epithelium and its surrounding stroma could help us in developing metastatic models of prostate carcinogenesis. This concept will allow us to define epithelial-specific markers, markers induced as the result of stromal-epithelial interaction, and stroma-associated markers. These markers together will assist us in diagnosing, preventing, prognosing and treating prostate cancer more efficaciously in the future.