Non-small cell lung cancer shows marked genetic and clinicopathological heterogeneity, which may explain its poor prognosis despite the continuous development of target therapy. Diagnosis of lung cancer is established by examination of small tissue specimens obtained by minimally invasive techniques. It is critical to employ these tissues at maximum efficiency in order to render an accurate pathologic diagnosis and to perform studies, either genomic or by immunohistochemistry, to demonstrate genetic mutations that make patients eligible for molecularly targeted agents.