Introduction: Primary lymphoma of the central nervous system (PLCNS) is a rare tumour whose incidence has increased substantially in immunocompetent patients. AIM. To examine the clinical and neuroimaging features in this risk group, with the aim of establishing a set of characteristics that can lead to a quick and accurate diagnosis., Patients and Methods: The study analysed all the cases of diffuse B-cell PLCNS that had been diagnosed histologically over the past 13 years in two neurological, neurosurgical and oncological referral hospitals in the north-east of the country. RESULTS; A total of 38 patients were studied (age: 15-84 years old), 55.3% of whom were males. The most frequent clinical presentation was gait instability, speech disorders and headache. The analysis showed that 94.7% of the lesions are supratentorial, and 68% have deep-structure involvement. In magnetic resonance imaging, 50% show homogeneous lesions, 94.7% were T₁ hypo/isointense and 65.8% were T₂ hyperintense, the mean size being 2.97 cm. Computerised tomography showed 48% of the lesions to be hyperdense. All the patients displayed enhancement following the administration of contrast. The overall median time of survival is 209 ± 134.85 days., Conclusions: PLCNS can manifest a number of different features per image, which have gradually changed over time, and we must be familiar with them in order to establish a quick diagnosis. Intensive efforts must be made to improve sensitivity and diagnostic specificity, and to conduct research on the biological mechanisms, the possible risk factors and the prevention of iatrogenic neurotoxicity.