It is frequently recognized in medical literature as well as in daily clinical practice that right ventricular myocardial infarction and pulmonary embolism are two of the most challenging clinical pictures to differentiate in cardiology and the treatment, often chosen upon a mixture of clinical suspicion criteria subsequently confirmed by other diagnostic methods, can lead to therapeutic success. Differential diagnosis is often difficult due to similar clinical picture, unspecific electrocardiographic changes and unspecific biological markers. It is very important to know the risk factors and the associated comorbidities for these two clinical entities in order to be able to interpret them contextually. In most cases the diagnosis key is the clinical suspicion. Usually in evaluating these cases we are in the position of choosing more complex diagnostic procedures, most likely not available in Emergency Department. In conclusion it is expected from the clinician to use the available methods with a thorough approach to details but in the same time considering the whole clinical picture.