The objectives of the study are to assess the impact of HIV status on the outcome of patients with non-small-cell lung cancer (NSCLC) in the era of highly active antiretroviral therapy (HAART). Patients diagnosed with HIV-related NSCLC in the HAART era (since January 1996) were identified from a prospective single-centre lung cancer database. The clinicopathological characteristics and outcome of each HIV-positive patient were compared to three age- and stage-matched HIV-negative controls with NSCLC who were diagnosed over the same time period and treated in an identical manner. The results showed that the two groups had similar disease characteristics and received a similar amount of chemotherapy. The median overall survival of the two groups was the same (4 months, log rank P=0.55). None of the HIV-positive patients developed an AIDS defining illness or died of HIV during treatment or follow-up. In conclusion, in this cohort, HIV status does not influence the prognosis of advanced NSCLC. This suggests that the survival of patients with HIV-related NSCLC may have improved since the introduction of HAART, and this may be due to a decrease in HIV-related deaths.