Objective: Adenosquamous carcinomas of the lung constitute a rare and aggressive variant of lung cancers. The pressing interest in evaluating the mutational status in lung carcinomas for predicting responsiveness to targeted therapies is presently focused on adenocarcinomas (of different sub-types), which makes preliminary histological typing a crucial step in order to select cases to be genetically analyzed. Hence the interest in deciding if adenosquamous carcinomas should be included among adenocarcinomas or, viceversa, if they should be interpreted as a variant of squamous cancers and excluded from the process of gene analysis. Method: We have thus collected, from our two Institutions a large number (45 cases) of cancers showing the histological definition of adenosquamous carcinomas according to the WHO criteria and performed gene analysis for k-RAS (codons 12, 13) and EGFR (codons 18, 19 and 21) mutations. The detection of rearrangements of the ALK gene by FISH was also performed.