An elevated platelet count may occur during care of neurology/neurosurgical patients and is usually due to reactive or secondary thrombocytosis (ST) caused by inflammation or infection. Primary (clonal) thrombocythemia or essential thrombocythemia associated with myeloproliferative disorders is usually known before or during early patient assessment. Rarely, paraneoplastic causes of thrombocytosis may be discovered. Although no single test differentiates primary from secondary etiologies, laboratory tests that show increased acute phase responses, such as C-reactive protein, fibrinogen, erythrocyte sedimentation rate, and interleukin-6, may be useful in diagnosing ST. Thrombosis due to ST is rare in any platelet count. ST, however, should be considered within the overall risk assessment for thromboembolism in any patient. If treatment is initiated, low-dose aspirin is sufficient.