Despite decades of research and an enormity of resultant data, cancer remains a significant public health problem. New tools and fresh perspectives are needed to obtain fundamental insights, to develop better prognostic and predictive tools, and to identify improved therapeutic interventions. With increasingly common genome-scale data, one suite of algorithms and concepts with potential to shed light on cancer biology is phylogenetics, a scientific discipline used in diverse fields. From grouping subsets of cancer samples to tracing subclonal evolution during cancer progression and metastasis, the use of phylogenetics is a powerful systems biology approach. Well-developed phylogenetic applications provide fast, robust approaches to analyze high-dimensional, heterogeneous cancer data sets. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.