Venous thromboembolism (VTE) is a major cause of morbidity and mortality among hospitalized patients. Studies have reported an incidence of deep venous thrombosis to be as high as 50%, especially after craniotomy. Several factors are involved in the alteration of the specificity and sensitivity of D-dimer testing. These include symptom duration, the extent of fibrinolytic and thrombosis activity, anticoagulant therapy, comorbidity associated with medical or surgical illness, cancer, inflammatory diseases, old age, postpartum, and pregnancy period, as well as previous VTE. Several studies have shown the high sensitivity of the D-dimer test (>95%) in pulmonary embolism or acute deep venous thrombosis. The cut-off value is usually within the 500 µg FEU/L range, ruling out acute VTE, especially in patients with low or intermediate clinical probability. Patients who present with a high D-dimer level may necessitate an intense diagnostic approach, the pretest probability notwithstanding. Herein, we present a case of a 52-year-old male patient who presented with a normal D-dimer level in deep venous thrombosis.