The present invention provides methods and compositions involving detecting the presence of and/or assessing the risk of cancer in a subject. These methods include methods of detecting and diagnosing cancer in an individual; methods of identifying individuals at risk of developing a cancer; and methods of staging a cancer. The methods generally involve detecting a palladin gene nucleotide sequence alteration that has been found to be associated with cancer and/or detecting a level of a palladin mRNA and/or protein in a biological sample. The present invention further provides nucleic acid probes, nucleic acid primers, and antibodies, as well as kits comprising one or more of the same, for use in a subject method.