No universal, specific diagnostic test exists for Marfan syndrome despite the identification of the causative gene. A diagnosis is made based upon a detailed patient and family history, a thorough clinical evaluation, and a variety of specialized tests performed to identify key findings associated with Marfan syndrome. Different criteria have been proposed for classifying someone as having Marfan syndrome. The most recent published criteria (the revised Ghent nosology) were published in 2010. According to these guidelines, the presence of aortic root aneurysm, eye lens dislocation, or a family history of definite Marfan syndrome weigh heavily in the diagnosis of Marfan syndrome, with an additional potential contribution of other findings throughout the body. Molecular testing (e.g. looking for a mutation in the FBN1 gene) can aid in the diagnosis of Marfan syndrome, but identifying a mutation is not sufficient to establish the diagnosis in the absence of sufficient physical findings.

Individuals suspected of having Marfan syndrome will usually undergo a complete skeletal examination, a heart examination including a test that uses sound waves to produce images of the heart (echocardiogram), and a specialized examination of the eyes (slit-lamp eye examination). A slit-lamp allows an eye doctor to examine the eyes under high magnification to detect lens dislocation and other eye issues. It is essential that this comprehensive diagnostic evaluation be coordinated by someone very familiar with Marfan syndrome and related diagnoses.