Fecal immunochemical tests (FITs) for hemoglobin represent a major advance over guaiac-based fecal occult blood tests (GFOBTs) for colorectal cancer screening. FITs specifically detect human hemoglobin in stool samples, whereas GFOBTs only detect heme. Studies show that FITs increase the detection rates of cancer and advanced adenoma compared with early-generation GFOBTs, and do so without the unacceptably high number of colonoscopies that high-sensitivity GFOBTs generate. Also, FITs are simpler to use than GFOBTs, they improve rates of patient participation, and their cut-off points for positive versus negative tests can be modified. A large, Dutch, population-based, randomized controlled trial has compared the performance of a GFOBT and a FIT on an intention-to-screen basis. This study found that the FIT detected two-and-a-half times as many cancers and advanced adenomas as did the GFOBT, despite similar colonoscopy rates. The latest generation of FITs should replace traditional GFOBTs in two-step (test then colonoscopy) screening for colorectal cancer.