The 4-day combination of dexamethasone, ifosfamide, cisplatin, and etoposide (DICE) is a salvage regimen for lymphoma. We report a prospective phase II multi-center trial of a modified DICE regimen in relapsed or refractory Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), constituting a single day of intravenous administration followed by 3 days of oral administration, aimed at reducing inpatient days without losing efficacy. Forty patients (median age 56, range 25 - 79) were included: 28 (70%) NHL, 9 (23%) HL and 3 (8%) CLL. Fifty-three per cent had received 2 prior treatment regimens. International Prognostic Index (IPI) was 2 in 75% of NHL patients. Patients aged 55 and those with previous autologous stem cell transplantation (ASCT) started on a lower-dose regimen, with dose escalation possible in 2 patients. Overall response rate was 41%. Thirty-eight per cent of patients had stable disease. With a median of 3.1 years of follow-up, estimated progression-free survival (PFS) and overall survival (OS) rates at 3 years were 15% and 43% respectively. OS was longer in the < 55 compared to the 55 age cohort (P = 0.0091), longer for HL than NHL (P = 0.59 and 0.039 respectively) and longer for Low/Low-Int IPI than High/High-Int IPI (P = 0.0074 and 0.0009 respectively). Median duration of inpatient stay was 3 days. There were no treatment-related deaths. In conclusion, this modification of DICE is an effective and well tolerated salvage regimen, even in this poor prognosis group of patients. Further clinical studies of DICE in first relapse and in older patients, possibly with the addition of rituximab, are warranted.