In one aspect, the invention is directed to a method of detecting Cowden syndrome (CS) or CS-like syndrome in an individual comprising detecting the presence of a mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof in the individual, wherein detection of a mutated SDHB, SDHD or a combination thereof indicates that the individual is positive for CS or CS-like syndrome. In another aspect, the invention is directed to a method of determining whether an individual is at risk for developing Cowden syndrome (CS) or CS-like syndrome comprising detecting the presence of a mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof in the individual, wherein detection of a mutated SDHB, SDHD or a combination thereof indicates that the individual is at risk for developing for CS or CS-like syndrome. In yet another aspect, the invention is directed to an article of manufacture for detecting Cowden syndrome (CS) or Cowden-like syndrome in an individual, comprising one or more agents that detects mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof in the individual, and instructions for use.