The reproducibility of mass spectrometry proteomic profiling has become an intensely controversial topic. The mere mention of concern over the reproducibility of data generated from any particular platform can lead to the anxiety over the generalizability of its results and its role in the future of discovery proteomics. In this study, we examine the reproducibility of proteomic profiles generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) across multiple data-generation sessions. We analyze the problem in terms of the reproducibility of signals, reproducibility of discriminative features and reproducibility of multivariate classification models on profiles for serum samples from early lung cancer and healthy control subjects.