Background: TP53 is one of the most commonly altered genes in lung adenocarcinoma, with as many as 50% of all cases possessing somatic inactivating mutations. Germline mutations in TP53 predispose to a wide variety of cancers in Li-Fraumeni syndrome. While lung cancer is generally not considered a classic Li-Fraumeni malignancy, several studies have indicated it may appear at an earlier age in this cancer-prone syndrome. Methods: We tested the frequency of germline TP53 mutations in an unselected cohort of lung adenocarcinoma cases sequenced as part of The Cancer Genome Atlas (TCGA) project. At the time of data access (October 1, 2014), germline exome and genome data were available for download from 531 subjects, and clinical information was available on 94% of these cases (n = 497). After Data Access Committee approval, we extracted raw bam files that included the TP53 sequence, called and annotated the variants. We considered variants with high (greater than 20x) coverage, and then excluded those with a minor allele frequency of 0.005 or greater in control populations. Suspected pathogenic variants were then confirmed by examining the matched tumor sequence data or a replicate normal tissue sample using the same methods. Results: Four cases carried germline missense variants in TP53 (0.8%), and all of them fell in the DNA binding domain. Three of the mutations were previously described in Li-Fraumeni syndrome and all of mutations have been reported as somatically mutated in various cancers. The mean age at lung cancer diagnosis was 58 years (range 41-73) and one individual was male. One of the cases was a never smoker (female), and another subject had a prior history of thymic carcinoma, a diagnosis that has been documented in Li-Fraumeni syndrome. Conclusions: Our data suggest that a subset of lung adenocarcinoma patients carry germline mutations in TP53, pointing to a role for inherited factors in lung cancer susceptibility. This diagnosis may be overlooked in cases where genomic data is filtered for background germline variants, and is relevant for genetic counseling and screening decisions.