Patients with primary central-nervous-system lymphoma (PCNSL) are treated with chemotherapy and cranial irradiation, which increase the risk of late neurotoxicity. The aim of this phase II trial was to investigate whether chemotherapy alone could induce durable remissions. Thirty non-immunocompromised patients were enrolled in two treatment groups, according to age. Patients in group A (< 65 years; n = 17) received carmustine, vincristine, dexamethasone, high-dose methotrexate and high-dose cytarabine. Patients in group B > 65 years: n = 13) were treated with carmustine, vincristine, dexamethasone and high-dose cytarabine. Both groups received intrathecal treatment. Radiotherapy was reserved for patients with stable or progressive disease. The overall response rate in group A was 65% (complete response 35%; partial response 29%) and in group B. 61% (complete response 23%; partial response 38%), but only 6 remissions were maintained without irradiation. In all, there were five treatment-related deaths. Responses were induced, but were mostly of short duration, and the treatment was associated with profound toxicity.