Activated Leukocyte Cell Adhesion Molecule (ALCAM) has been linked to the progression of numerous human cancers, where it appears to play a complex role. The current study aims to further assess the importance of ALCAM in prostate cancer and the prognostic potential of serum ALCAM as a biomarker for prostate cancer progression. Here we demonstrate enhanced levels of tissue ALCAM is associated with metastasis. Additionally, elevated serum ALCAM is indicative of progression and poorer patient outlook, and demonstrates comparable prognostic ability to PSA in terms of metastasis and prostate cancer survival. ALCAM suppression enhanced proliferation and invasiveness in PC-3 cells and motility/migration in PC-3 and LNCaP cells. ALCAM suppressed PC-3 cells were generally less responsive to HGF and displayed reduced MET transcript expression. Furthermore a recombinant human ALCAM-Fc chimera was able to inhibit LNCaP cell attachment to HECV and hFOB1.19 cells. Taken together, ALCAM appears to be a promising biomarker for prostate cancer progression, with enhanced serum expression associated with poorer prognosis. Suppression of ALCAM appears to impact cell function and cellular responsiveness to certain micro environmental factors.