Follicular lymphoma is a low grade malignant lymphoma. However, some follicular lymphomas undergo histological transformation into higher grade malignant lymphomas. We recently encountered a diffuse large cell lymphoma which seemed to have progressed from a follicular lymphoma and which finally transformed into a small non-cleaved lymphoma. Each stage of the histological transformation was accompanied by increasing clinical grades of malignancy. It was suspected that in our patient a follicular lymphoma initially developed due to rearrangement of the BCL2 gene, and then underwent histological transformation into a diffuse large cell lymphoma, which was associated with p53 mutation. Subsequent rearrangement of C-MYC promoted the histological transformation of this diffuse large cell lymphoma into a small non-cleaved lymphoma. Our findings indicate that p53 mutation and rearrangement of C-MYC are involved in the histological transformation of follicular lymphomas into more advanced lymphomas.