IgG4-related disease (IgG4-RD) has been accepted as a distinct entity in various fields. It is being increasingly diagnosed and treated in routine practice. However, difficulties are still associated with the diagnostic process. Serum IgG4 elevations and imaging studies are useful, but not entirely diagnostic for this condition. Therefore, a pathological examination still plays an important role. Three characteristic microscopic changes are dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. IgG4 immunostaining reveals many IgG4-positive plasma cells and an IgG4/IgG-positive cell ratio of more than 40%. In addition to the number and ratio of IgG4-positive plasma cells, the diffuse distribution of positive plasma cells needs to be confirmed because IgG4-positive plasma cells may focally aggregate in many other conditions. In small biopsy samples, it is important to recognize not only characteristic findings, but also microscopic changes that are unlikely to occur in IgG4-RD because the identification of the latter findings leads to the exclusion of this condition. Another challenging field regards the diagnosis of long-standing disease. Along with disease progression, inflammatory infiltrate decreases, while storiform fibrosis and obliterative phlebitis are suspected to persistently exist. Therefore, the recognition of the latter two findings will be a diagnostic clue. Given the general suspicion that IgG4-RD has recently been over-diagnosed, precise tissue examinations based on the proposed standards and close clinicopathological correlations are crucial.