We have reported that [111In]T101 is highly effective in the detection of cutaneous T-cell lymphoma (CTCL) in nodal and cutaneous (erythroderma and tumor) sites. This study compares the biodistribution of [131I]T101 (1 to 7.1 mg, 2 mCi) in four patients with CTCL; two of these patients also received [111In]T101 (1 mg, 5 mCi). There was rapid clearance of [131I]T101 from whole-body, spleen, liver, and bone marrow, with evidence of loss of 131I tracer from the T101. Lymph node uptake was minimal in three of four patients, and there was no localization in skin lesions. This contrasted with [111In]T101 where there was prolonged retention of activity in these organs and excellent uptake in skin tumors, erythroderma, and lymph nodes. The study showed that [131I]T101 was suboptimal for imaging CTCL patients and demonstrates that the isotope or labeling method can dramatically alter the apparent biodistribution and tumor targeting of a given monoclonal antibody.