Rheumatology is a clinically oriented specialty. All laboratory tests need to be interpreted in light of the clinical picture since tests, viewed in isolation, can be misleading. Rheumatoid Factor (RF) is seen in several conditions, including Rheumatoid Arthritis (RA). A positive RF does not mean RA. A negative test does not exclude RA. Indirect immunofluorescence (IIF) is the preferred test methodology for Antinuclear antibodies (ANA). A negative ANA on IIF virtually rules out systemic lupus erythematosus (SLE) because ANA-negative SLE is very rare in clinical practice. A positive test may or may not confirm SLE and needs clinical correlation. Antibodies to extractable nuclear antigen (ENA) should only be obtained in patients with positive ANA. Antiphospholipid syndrome is a clinico-serologic diagnosis that requires clinical features in addition to antiphospholipid antibodies. Antistreptolysin O should not be used as the only basis for diagnosing rheumatic fever. ELISA is the preferred test methodology for Antineutrophil cytoplasmic antibody (ANCA) detection. ANCA should not be used as a screening test. A high serum uric acid does not translate into a diagnosis of gout. Hyperuricemia is a biochemical abnormality while gout is a clinical syndrome. Synovial fluid examination is an important yet infrequently ordered test. It is invaluable in monoarthritis. HLA B27 is present in a significant proportion of the healthy population, the majority of whom will never develop SpA.