Patients presenting with isolated partial cervical myelopathy are at high risk for development of multiple sclerosis (MS), especially if lesions suggestive of demyelination are present on cranial magnetic resonance imaging (MRI). This risk is lower, though not precisely known, in patients whose cranial MRI is normal. This clinical issue was addressed by examining the role of paraclinical studies in establishing a diagnosis of MS at the time of initial presentation. Twelve consecutive patients, mean age of 32.2 years, seen over 6.5 years were identified prospectively and included in this study. Numbness was the presenting symptom in 11 of these patients. Symptoms completely resolved in nine patients regardless of treatment with glucocorticoids. Evoked potential (EP) and cerebrospinal fluid (CSF) examinations assisted in establishing a diagnosis of laboratory-supported definite (LSDMS) or clinically probable (CPMS) MS in six patients at the time of presentation. During a clinical follow-up period of 4.1 years, four developed recurrent neurologic deficits leading to the establishment of a diagnosis of clinically definite MS (CDMS). The presence of a solitary, non-specific lesion on cranial MRI resulted in an increased risk for the development of definite MS. In patients with a clinically isolated cervical partial transverse myelitis (TM) and normal cranial MRI, an accurate diagnosis of MS can usually be made. Revision of the diagnostic criteria for LSDMS is warranted.