The presentation of Foundations in Cancer Research articles has become a focal point of the Advances in Cancer Research series. This volume begins with two such timely reviews, the first of which is by series co-editor George Klein. Dr. Klein evaluates and reviews Leslie Foulds’ suggestion that tumors develop in a series of steps and the effect that this 40-year-old hypothesis has had on cancer research. The second Foundations article by L.A. Loeb presents the historical significance of increased mutagenesis and clonal selection on tumor progression. The first regular article, by R. Khosravi-Far and colleagues, analyzes the functional role of Ras in signal transduction and the involvement that Rho family proteins have on Ras. Mark Saville and Roger Watson review supporting evidence that B-Myb may be a critical regulator of the cell cycle. S. Baylin and co-authors compare DNA methylation in normal cells with that in cancerous cells and discuss the specific consequences associated with tumor progression. Last, Steven Grant discusses the use of ara-C as a treatment for various types of cancer and summarizes its cellular metabolism, mode of action and resistance, and the molecular events involved in apoptosis.