Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare tumor type distinct from classical Hodgkin lymphoma and its familial form is unusual. The two cases ( mother at age 48 and son at age 30 years) of NLPHL in advanced clinical stage are described. The patients were successfully treated with an immunochemotherapy schedule consisting CHOP plus rituximab (CHOP-R). This chemotherapy was well tolerated and the patients reached complete remission. These remissions were for 34 and 40 months for mother and son, respectively. In patients with NLPHL, CHOP-R regimen should be used as an alternative treatment regimen to obtain a good long-lasting response without any adverse events.