Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is subdived into 2 major histological subtypes: adenocacinoma (ADC) and squamous cell carcinoma (SCC). Super-SILAC methodology was used to facilitate the quantitative comparisons of human primary tumor-derived xenograft proteomes by high resolution MS analysis. Xeno092 and Xeno441 were ADCs. Xeno 561 and Xeno691 were SCCs. Principal component analysis and supervised t-tests revealed differentially expressed proteins responsible for the classification of the samples according to their distinctive proteomes. These results confirm known differentiators between ADC and SCC subtypes of NSCLC (e.g. a keratin signature, cell adhesion molecules, and metabolism proteins), and reveal novel candidates that may be useful to classify and treat NSCLC tumors. The raw files were analyzed by MaxQuant (version 1.3.0.5). Peaks were searched against the UniProt human database (released Jul, 2012; http://www.uniprot.org) using the Andromeda search engine included in MaxQuant. Two miscleavages were allowed and at least six amino acids per identified peptide were required. The false discovery rate for peptides and proteins was set at 0.01. 'Match between runs' option was selected within a time window of 2 min. A minimum ratio count of 2 was used for quantification of SILAC pairs. Further data analysis was performed in Perseus.