Colorectal cancer may develop slowly over years from precursor lesions, and thus screening combined with early diagnosis is the key to disease prevention. Recent studies have elucidated specific traits in the gut microbiome associated with colorectal cancer and suggested that the microbiome may be useful in screening for colorectal cancer purposes but failed to provide protocols that can be applied in a practical situation. A recent study by Zackular and colleagues, presented on page 1112, provides an important way forward here in showing that specific analysis of multiple aspects of the microbiome composition in toto provides reliable detection of both precancerous and cancerous lesions. This important achievement when combined with other noninvasive techniques promises to provide highly effective tools for early colorectal cancer diagnosis and its prevention. (C) 2014 AACR.