BACKGROUND: Basal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic. OBJECTIVE: The goal of this study was to assess how immune-cell related gene expression in an initial BCC tumor biopsy was related to the appearance of subsequent BCC tumors. MATERIALS AND METHODS: Levels of mRNA for CD3ε (a T-cell receptor marker), CD25 (the alpha chain of the interleukin (IL)-2 receptor expressed on activated T-cells and B-cells), CD68 (a marker for monocytes/macrophages), the cell surface glycoprotein intercellular adhesion molecule-1 (ICAM-1), the cytokine interferon-γ (IFN-γ) and the anti-inflammatory cytokine IL-10 were measured in BCC tumor biopsies from 138 patients using real-time PCR. RESULTS: The median follow-up was 26.6 months, and 61% of subjects were free of new BCCs two years post-initial biopsy. Patients with low CD3ε CD25, CD68, and ICAM-1 mRNA levels had significantly shorter times before new tumors were detected (p = 0.03, p = 0.02, p = 0.003, and p = 0.08, respectively). Furthermore, older age diminished the association of mRNA levels with the appearance of subsequent tumors. CONCLUSIONS: Our results show that levels of CD3ε, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new BCC tumors.