Endocannabinoids have been shown to modulate key cell-signaling pathways involved in cancer cell growth, invasion and metastasis. In spite of cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, their effects on cell proliferation in cancer cells is still controversial. The aim of this study was to investigate the anandamide (AEA) effect in LNCaP and PC3 prostate cancer cells, evaluating cell proliferation by FACS analysis and the induction of two proto-oncogenes by quantification of the expression level of cPLA₂ and c-fos genes. In the present study we have analyzed, by PCR and FACS, the effect of 5 mM AEA on the expression level of c-PLA2 and c-fos genes mRNA, and on cell cycle progression of LNCaP and PC3 prostate cancer cells. AEA treatment induced cell proliferation and an increase of cPLA2 expression after 3 h in both cell types. The expression of c-fos gene was enhanced after 12 h growth in LNCaP cells, and after 24 h in PC3 cells. Our data indicate that AEA could act as a mitogen, contributing to cancer progression; therefore, it is important to reconsider the use of these compounds in clinical treatments.