Systemic sclerosis presents a great deal of variability among different patients in the extent of skin and internal organ involvement, the pace of the disease and consequently, the prognosis. In addition, the single patient, during his/her disease course, can present with distinct manifestations. Each patient must, therefore, be carefully investigated. The assessment should be adapted to the setting, i.e. clinical practice, clinical investigation, therapeutic trials. The clinician cannot confine the diagnostic process to labelling the disease. He must define the subset, the extent of internal organ involvement, and the type of lesions underlying the clinical manifestations, i.e. fibrotic lesions, reflecting irreversible damage should be separated from active lesions (such as alveolitis) which can be reversed by drug treatment. The clinical investigator must assure that his/her patients are comparable to other series. ACR criteria have been shown to not assure such comparability. To this purpose, a core set of variables to be assessed in any clinical investigation study has been proposed. Finally, the clinical researcher should enrol patients with active disease and must rely for his/her conclusions on feasible and sensitive to change measures. An OMERACT committee has recently reviewed the literature selecting those ready for use in clinical trials.