Background: Pulmonary adenosquamous carcinoma (ASC) is a rare type of lung cancer containing both adenocarcinoma (AC) and squamous cell carcinoma (SCC) cells. To better understand the mechanism by which the AC and SCC components are involved in lymph node metastasis, we evaluated the distribution of these cellular components in both primary ASC tumors and lymph node metastases. Methods: Twenty-two patients with ASC and 142 with AC were admitted to the First Affiliated Hospital of Sun Yat-sen University between July 2006 and July 2012 and underwent surgical resection. Primary ASCs and lymph nodes, with or without metastasis, were assayed immunohistochemically for TTF-1, p63, p40, and VEGF-C. Results: The incidence of lymph node metastasis was higher in patients with ASCs than ACs; however, other features of ASC and AC showed no differences. ASC tumors were positive for TTF-1, p63, and p40; however, these proteins were distributed in different tumor islands in the same tumor. Co-expression was less frequent, but TTF-1 expression was higher in metastatic lymph nodes. Conclusions: ASCs are highly aggressive tumors that metastasize via the lymphatic pathway. The two cellular components of these tumors (AC and SCC) behave independently, with the AC component playing a predominant role in lymphatic invasion. Metastatic lymph nodes should be evaluated immunohistochemically to choose a proper chemotherapeutic strategy in patients with ASCs.