Purpose: Personalized medicine is predicated on the concept of identifying subgroups of a common disease for better treatment. Identifying biomarkers that predict disease subtypes has been a major focus of biomedical science. In the era of genome-wide profiling, there is controversy as to the optimal number of genes as an input of a feature selection algorithm for survival modeling. Patients and methods: The expression profiles and outcomes of 544 patients were retrieved from The Cancer Genome Atlas. We compared four different survival prediction methods: (1) 1-nearest neighbor (1-NN) survival prediction method; (2) random patient selection method and a Cox-based regression method with nested cross-validation; (3) least absolute shrinkage and selection operator (LASSO) optimization using whole-genome gene expression profiles; or (4) gene expression profiles of cancer pathway genes. Results: The 1-NN method performed better than the random patient selection method in terms of survival predictions, although it does not include a feature selection step. The Cox-based regression method with LASSO optimization using whole-genome gene expression data demonstrated higher survival prediction power than the 1-NN method, but was outperformed by the same method when using gene expression profiles of cancer pathway genes alone. Conclusion: The 1-NN survival prediction method may require more patients for better performance, even when omitting censored data. Using preexisting biological knowledge for survival prediction is reasonable as a means to understand the biological system of a cancer, unless the analysis goal is to identify completely unknown genes relevant to cancer biology. © 2013 Kim and Bredel, publisher and licensee Dove Medical Press Ltd.