All diseases including autoimmune diseases, chronic liver diseases and cancer are a serious health problem worldwide. The current gold standard to assess malignant changes in cells and structural liver damage is through a biopsy, which has several disadvantages. A non-invasive simple test to diagnose malignancy and liver pathology would be highly desirable. Protein glycosylation has drawn the attention of many researchers with an aim to achieve this goal. Glycosylation is the post-translational modification of many secreted proteins and it has been known for decades that structural changes in the glycan structures of serum proteins are an indication of carcinogenesis and liver damage. The aim of this paper is to give an overview of the altered protein glycosylation in different etiologies of liver diseases, autoimmune diseases, and cancer. Although individual carcinoma and liver diseases have their own specific markers, the same alteration seems to reappear continuously in all malignant transformation and liver diseases like hyperfucosylation, sialylation, increased branching and bisecting N-acetylglucosamine.