Background: The association of aryl hydrocarbon receptor (AhR) overexpression with cytochrome P450 1B1 (CYP1B1) expression is commonly detected in non-small cell lung cancer (NSCLC). In vitro and animal studies have shown an interaction between AhR and p53, or the epidermal growth factor receptor (EGFR). The clinical importance of AhR or CYP1B1 overexpression, however, as well as the relationship between AhR and p53 or EGFR in lung carcinomas, remains unclear. Patients and Methods: Immunohistochemistry for AhR, CYP1B1, EGFR and/or p53 expression was performed on two tissue microarrays containing 152 NSCLC specimens. Results: High levels of CYP1B1, EGFR and p53 expression were more prevalent in stage-IV disease than in earlier stages (OR, 6.0; 95% C.I., 2.25-15.90), whereas AhR was not. The AhR expression, but not CYP1B1, was associated with both the EGFR (p=0.040) and p53 expression (p=0.026). The expression of AhR and CYP1B1 did not affect the survival of NSCLC patients. Conclusion: CYP1B1, EGFR and p53 overexpression are considered to be aggressive biomarkers for NSCLC, indicating that early-staged patients warrant an aggressive treatment when these factors are overexpressed in the cancer cells.