Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). The recognition of typical morphological features usually allows to distinguish CD from UC. Several infectious diseases like tuberculosis as well as other disorders can mimic IBD and need to be excluded before immunosuppressive treatment is started or surgical intervention planned. IBD is associated with an increased risk for the development of colorectal adenocarcinoma. There is a strong relationship between the presence of intraepithelial neoplasia (IEN) in patients with CD or UC and colon cancer. Thus, the differentiation between biopsies with reactive atypia, low-grade IEN and high-grade IEN is of great importance. Furthermore, distinction between dysplasia-associated lesions or masses (DALM) and sporadic adenoma-like masses (ALM) is crucial as prophylactic colectomy is usually recommended for DALM and polypectomy may be sufficient for ALM. Various features like localization of the lesion, architecture, inflammation and immunohistochemical evaluation of additional markers, e.g. p53 and beta-catenin, may be helpful in the distinction of DALM versus ALM. Finally, the use of modern immunosuppressive therapies may go along with an increased susceptibility towards infections, e.g. cytomegalovirus colitis or Epstein-Barr virus-induced lymphoproliferative disorders, and a high degree of awareness by clinicians and pathologists is required in order not to miss these life-threatening complications of IBD.