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Serum and plasma differ by the presence of clotting proteins. Serum is the liquid fraction remaining after blood has clotted; fibrinogen is consumed in the clotting process, and many coagulation factors are depleted or inactivated. Plasma is obtained from anticoagulated blood after centrifugation and retains fibrinogen and other coagulation proteins. Thus, Option B accurately describes the distinction. Option A reverses definitions. Option C misstates additives; anticoagulants (e.g., EDTA, citrate, heparin) are in plasma tubes, not serum tubes. Option D is incorrect because certain assays specifically require one matrix: coagulation studies require citrated plasma, many chemistry assays accept either but may have method-specific validation, and some immunoassays prefer serum. Understanding these matrices guides correct tube selection (e.g., gold/tiger-top SST for serum, green for heparinized plasma, lavender for EDTA whole blood) and prevents analytic errors. Proper inversion after draw ensures anticoagulant efficacy in plasma tubes, while serum tubes must clot fully before processing. Mastery of these fundamentals underpins accurate specimen collection and is routinely assessed on phlebotomy certification exams.