Immune mediated inflammatory diseases (IMIDs) are a diverse range of diseases that affect joints with early overlapping symptoms. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are the most common disorders sharing immune-pathogenic mechanisms that cause peripheral arthritis. Psoriasis (Ps) is a chronic inflammatory autoimmune skin disease characterized by epidermal hyperplasia with significant invasion by inflammatory cells. New biomarkers are required to enable an early diagnosis and differentiation between different types of IMIDs. In autoimmune disorders, galectin 1 (Gal-1) is a recognized as negative immune system regulator. This study aimed to determine the possibility of using gal-1 as a diagnostic marker to differentiate between RA and PsA with polyarthritis pattern, and between PsA and Ps, and to assess its relationship with disease activity and with skin lesion. In this case-control study included 40 PsA patients with polyarthritis pattern, 40 psoriatic patients, 40 RA patients and 20 normal controls. Gal-1 levels were measured in serum and skin biopsy and disease Activity Score (DAS-ESR) was assessed. Serum gal-1 level was significantly higher in RA group in comparison to PsA, psoriatic and control. In addition, compared to the normal group, psoriatic skin lesions from PsA and Ps patients had lower levels of gal-1. Serum gal-1 levels in the RA group did not correlate with other factors such as age, disease duration, deformity, extra-articular symptoms, or DAS-ESR. Furthermore, there was no correlation between the skin's level of gal-1 and psoriatic area and severity index (PASI) score, body surface area (BSA). In conclusion, serum Gal-1 concentration may serve as a diagnostic biomarker to distinguish between RA and PsA. However, it cannot assess activity or severity of RA, and cannot differentiate psoriatic lesion either from only Ps or PsA.