IgG4-RD is a relatively newly recognised condition that can affect multiple organs, leading to their dysfunction or destruction. Diagnosing and managing IgG4-RD is challenging due to its clinical and histopathological overlap with other conditions, including malignancies, infections and autoimmune diseases. Overlapping features can lead to delays or misdiagnoses, such as mistaking autoimmune pancreatitis for pancreatic cancer or sarcoidosis for IgG4-RD. Reliance on serum IgG4 levels, while helpful, can be misleading due to their non-specific nature and variability. Histopathological analysis is crucial, requiring recognition of hallmark features like storiform fibrosis, obliterative phlebitis and dense lymphoplasmacytic infiltration with IgG4-positive plasma cells. Misinterpretation of histology or sampling errors can further complicate diagnosis. IgG4-RD’s systemic nature necessitates comprehensive evaluation to identify multiorgan involvement, such as renal or pancreatic lesions accompanying orbital pseudotumours. Relapses are common, often due to premature discontinuation of maintenance therapy. Corticosteroids remain first-line treatment, but steroid-sparing agents like rituximab (therapy targeting B cells represents a precision medicine approach) are essential for long-term management to minimise side effects. Regular monitoring and a multidisciplinary approach are critical to prevent complications such as irreversible organ damage.