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Background: Activated Leukocyte Cell Adhesion Molecule (ALCAM) is expressedin different kinds of normal and neoplastic tissues. Data on the tissue distribution of ALCAM suggestthat this protein is involved in tumor progression and metastasis. The lack of available data on ALCAMprotein expression in breast cancer prompted us to undertake a study on the involvement of this adhesionmolecule in tumor development. Material/Methods: The expressions of ALCAM and reference biomarkers wereexamined in 56 breast cancer specimens by laser scanning cytometry and confocal microscopy. The resultswere related to clinical and pathological parameters, i.e. histological grade, tumor diameter, lymphnode involvement, NPI, steroid receptor (estrogen, ER, and progesterone, PgR) expression, and HER2/neu over-expression. Results: High levels of ALCAM significantly correlated with small tumor diameter (p=0.009),low tumor grade (p=0.001), and the presence of progesterone (p=0.009) and estrogen (p=0.006) receptors.Declining ALCAM concentrations correlated with HER2/neu gene amplification, inasmuch as the obtainedp value, 0.065, was very close to the established statistical significance level of p=0.05. The ALCAM/MMP-2ratio was significantly higher in cancer cases characterized by small tumor size (p=0.04) and low tumorgrade (p=0.022). Conclusions: Analysis of ALCAM expression in relation to other molecular biomarkersrevealed that ALCAM expression and the ALCAM/MMP-2 ratio are more promising indicators of breast cancerprogression than MMP-2, E-cadherin, and alpha-catenin. Low ALCAM concentration correlated with an aggressivetumor phenotype, which supports the view that this adhesion molecule is a tumor suppressor marker withprognostic significance.