Molecular testing of pulmonary adenocarcinomas for EGFR and KRAS mutations is becoming more common as tyrosine kinase inhibitor therapy is used for EGFR-mutated adenocarcinomas. Adenosquamous carcinomas represent a hybrid carcinoma, and there is no literature addressing the frequency of EGFR and KRAS mutations in this subset of lung carcinomas in Western populations. For this study, 23 adenosquamous carcinomas were microdissected with the glandular and squamous components analyzed for EGFR and KRAS mutations and EGFR amplification. In 3 cases (13%), there were EGFR mutations, with 2 having the identical mutation in the glandular and squamous elements. In 3 cases (13%), there were KRAS mutations in both histologic elements. Great heterogeneity existed in the rates of EGFR amplification in the 2 histologic components. Amplification was most common in both glandular and squamous components (11/23 [48%]). EGFR mutations occur in adenosquamous carcinoma in the same percentages as in conventional adenocarcinoma in the Western population. KRAS mutations are less common.