Transforming acidic coiled-coil containing protein 3 (TACC3) is known to be involved in the control of normal cell growth and differentiation and in mechanisms of unregulated growth leading to tumorigenesis. The aim of the present paper was to determine the rate of TACC3 expression in a non-small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters. A total of 163 NSCLC were analyzed immunohistochemically using a polyclonal TACC3 antibody and monoclonal p53 and Ki-67 antibodies on NSCLC tissue microarrays. A high level of TACC3 expression was observed in 14.8% of cases, preferentially squamous cell carcinomas. Patients whose tumors had a high TACC3 expression had a significantly shorter median survival time. In the Cox regression-based multivariate analysis, TACC3 expression proved to be an independent prognostic parameter (P = 0.031). TACC3 expression was correlated with p53 expression, and patient whose tumors highly expressed TACC3 and p53 had a significantly poorer prognosis than patients whose tumors had low-level expression for both immunostainings (P = 0.006). It is suggested that increase in TACC3 may impart a proliferative advantage to NSCLC and contribute to tumor progression, and that TACC3 expression is a strong prognostic indicator of clinical outcome in NSCLC.