The frozen section diagnosis of lung nodules is difficult because inflammatory atypia and histologic artifacts can simulate a malignancy. From a total of 2,405 frozen sections examined, 143 cases were misdiagnosed or deferred, including 65 with reactive atypia (RA) and 35 bronchioloalveolar carcinomas or well-differentiated adenocarcinomas (BAC-AC), resulting in deferral and error rates of 4.36% and 1.58%, respectively. The presence of 25 pathologic features was evaluated by using an evidence-based pathology (EBP) approach. Of the pathologic features, 11 were significant at a P value of less than .05 but exhibited variable incidence in AC and RA. Positive likelihood ratios allowed for identification of the 5 most useful pathologic features for the diagnosis of AC: multiple growth patterns, anisocytosis, atypia more than 75%, macronucleoli, and atypical mitoses. Granulomas favored the diagnosis of RA. An EBP approach is helpful to stratify pathologic features according to their clinical applicability.