In a man presenting to the emergency room with dyspnea and atypical chest pain irradiated among the scapulae, with new-onset diffuse negative T-waves on the ECG, the first clinical and diagnostic hypothesis was pulmonary embolism (PE). However, computed tomography (CT) performed in emergency was negative for PE, showing instead a marked defect in right ventricle (RV) filling. For this reason, echocardiography was performed to better investigate the nature of the space-occupying lesion, and several echocardiographic modalities were used (two-dimensional transthoracic and transesophageal echocardiography and three-dimensional [3D] transthoracic echocardiography). They revealed the presence of a mass attached to the apex of the RV, partially obstructing the inflow and outflow tracts. Cardiac magnetic resonance imaging was also performed, confirming the findings of 3D echocardiography. After that, several other diagnostic imaging techniques were used for disease staging, since the patient had a history of surgical excision of a malignant melanoma of the skin several years before. Whole-body CT, soft tissue echography and positron emission tomography revealed the widespread diffusion of the primary tumor to distant organs. For this reason, we suspected that the RV mass could also be an intracardiac metastasis from malignant melanoma, and did not perform biopsy given the bad clinical conditions and the worse prognosis of the patient. However, he was entered in an experimental therapeutic protocol with Vemurafenib because he showed B-RAF gene mutation at molecular gene analysis.