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Colorectal cancer is one of the most common types of cancer with hereditary background. Due to the progress in DNA sequencing techniques, the number of identified cancers predisposing gene mutations is rising constantly. For some morphologically defined cancer predispositions like serrated polyposis, however, a genetic background is rarely identified. Even if this would exclude a hereditary predisposition, the elevated cancer risk remains, emphasizing the importance of histopathologic diagnoses.Hereditary colorectal cancer can be categorized into polypous and non-polypous predispositions. While the former elevate cancer risk by increasing the number of cancer precursors, the latter elevate cancer risk by increasing the likelihood of malignant transformation. It is the pathologist's responsibility to use morphologic criteria in combination with clinical data in order to raise suspicion of hereditary tumorigenesis and recommend genetic counselling. This article summarizes the current state of knowledge on hereditary colorectal cancer.The new German S3 guideline for colorectal cancer demands testing of all newly diagnosed colorectal cancers for Lynch syndrome association. Owing to this change in the guideline, this article will focus on diagnostic challenges of the DNA mismatch repair function.