Clonal Evolution in Follicular Lymphoma

* INCLUSION CRITERIA: * Histologically or cytologically confirmed follicular lymphoma (FL), grades 1-2, or 3a confirmed by the Laboratory of Pathology, NCI; patients who meet criteria for immediate initiation of systemic therapy are eligible * Adequate tissue available from original diagnostic biopsy. NOTE: If biopsy was \>12 months prior to enrollment OR adequate tissue is not available, tissue biopsy may be optionally repeated unless such a biopsy is considered unacceptable risk to the patient. Patients without adequate tissue are eligible at the discretion of the PI. \- Must have disease that is measurable or evaluable on either computed tomography (CT) scans or FDG-positron emission tomography (FDG-PET) scans NOTE: Since patients with FL may have lesions that wax and wane on imaging, the requirement for disease being measurable or evaluable can come from imaging taken at any time at or after diagnosis, the most recent imaging prior to enrollment does not need to show measurable or evaluable disease. \- Age greater than or equal to 18 years NOTE: Patients with the pediatric-type follicular lymphoma are usually \<18 years of age, and often have a very different clinical course than patients with the adult-type of FL. Due to this difference in biology, children are excluded from this study. \- ECOG performance status \<2 (Karnofsky \>60%) EXCLUSION CRITERIA: * Previous history of diffuse large B-cell lymphoma or histologic transformation * Any prior systemic treatment for lymphoma including cytotoxic chemotherapy, biologic therapy, and monoclonal antibody therapy (radiotherapy permitted); patients who have received chemotherapy, biologic therapy, hormonal therapy, or monoclonal antibody for other malignancies are potentially eligible provided that all of the following are true: a) that malignancy was not lymphoma, b) systemic therapy ended at least 3 years prior to the diagnosis of FL, and c) there is no evidence of active malignancy other than FL NOTE: Initiation of first-line systemic therapy is allowed while on this trial; concurrent participation in first-line treatment clinical trials will be permitted. * Patients who are HIV-positive * Any second malignancy that requires active systemic therapy * Any other (non-lymphoma) life-threatening disease * Patients unable to provide informed consent (surrogates will not be used) * Pregnant women are excluded from enrollment onto this study because the invasive procedures and/or sedation needed to perform them may cause unnecessary harm to the unborn fetus. In the event a woman becomes pregnant while on study, she will not be removed from the study; however, no follow-up invasive clinical or research procedures will be done that include unacceptable to risk to the patient and/or to the unborn fetus.