Pulmonary thromboembolism is a relatively common disease in an Emergency Department. Diagnosis, often difficult, is based on careful evaluation of risk factors, clinical examination, radiological and laboratory investigations. Plasma D-dimer, a degradation product of cross-linked fibrin with low specificity and very high sensibility, is considered extremely useful as screening to rule out a pulmonary thromboembolism. We report the case of a 74 year old woman who presented in the Emergency Department suffering from the sudden onset of dyspnea 4 hours before. Plasma D-dimer (automated latex-enhanced turbidimetric test) was normal (253 ng/mL; normal value: 278 ng/mL), but spiral CT angiography showed a sub-massive thromboembolism of the principal branch of the right pulmonary artery, also involving the middle and the inferior lobar branches. A cardiac echo-color-Doppler demonstrated an enlargement of the right cardiac section with telediastolic pressure in the pulmonary artery of 74 mmHg (normal value 4-12 mmHg). A second measurement of plasma D-dimer, 12 hours later, remained in the normal range (274 ng/mL) and only after four days was there a significant increase (1017 ng/mL). The authors, taking the case as a starting point, stigmatize the difficulties that such diagnosis involves, despite indications of guidelines.