The Early Detection Research Network (EDRN)/Canary Foundation tissue collection consisted of 60 lung adenocarcinoma tumors and matched adjacent histologically confirmed non-tumor lung (NTL), collected after surgery. Forty-five adenocarcinoma/NTL pairs were obtained from the Vancouver General Hospital (Vancouver, Canada) and 15 adenocarcinoma/NTL pairs from the British Columbia Cancer Agency Tumor Tissue Repository (Vancouver, Canada, BCCA Research Ethics Board #H09-00008). Thirty subjects were never-smokers (defined as less than 100 lifetime cigarettes), and 30 were current smokers (average 53 pack-years, range 11–120 pack-years). One tumor sample was excluded after pathology review later revealed it to be a large cell carcinoma. Subject characteristics for the remaining 59 subjects are detailed in Table 1. For verification of DNA methylation profiling, an independent sample set of 28 lung adenocarcinomas and 27 NTL was used. Subject characteristics for the validation population are detailed in Supplemental Table 2. Of these, 21 tumor and 20 NTL de-identified samples were purchased from the Ontario Tumor Bank (OTB, Ontario, Canada), while seven tumors and seven NTL were collected at the University Hospital at the University of Southern California (USC IRB protocol #HS-06-00447). For MethyLight verification of selected probes, OTB samples were used (26 tumors and 26 NTL), of which 25 pairs were matched. Ten of the tumors and 13 of the NTL samples examined by MethyLight were the same tissues used for the genome-wide verification. EDRN/Canary samples were assessed by an experienced pathologist (A.F.G.), while the verification samples were assessed by a separate expert lung pathologist (M.N.K.). All sample collections were performed conforming to protocols approved by the appropriate local Institutional Review Boards and were acquired with informed consent. The identities of the subjects were not made available to the laboratory investigators.