To investigate predictors of relapse in small (<or=1.5 cm) papillary thyroid cancers, we performed a retrospective chart review study of patients treated and followed up in our institution according a standard prospective protocol. Between 1975 and 2001, 299 patients were operated for a differentiated papillary thyroid cancer no larger than 1.5 cm in size. Near-total or total thyroidectomy was performed in 292 patients, and lobectomy in seven patients.Persistent/recurrent disease was observed in 77 patients; in 37 of these patients, the only sign was increased TSH-stimulated serum thyroglobulin (Tg). Ten patients developed distant metastases, and 68 locoregional metastases. At multivariate analysis, persistent/recurrent disease was associated with: 1) nonincidental thyroid cancer; 2) lymph node metastases at presentation; and 3) bilateral tumor. Development of distant metastases was associated with the sclerosant variant and the presence of lymph node metastases at presentation. Tumor size (<or=1.0 cm vs. 1.1-1.5 cm) was not predictive of relapse. No patient died because of the disease, but 14.4% had evidence of disease at their last follow-up visit. Serum Tg level below 1.0 ng/ml at the first postsurgical evaluation during l-T(4) withdrawal was an accurate predictor of no relapse. In conclusion, approximately one of four patients with a papillary thyroid cancer no more than 1.5 cm in size develops relapsing/persisting disease after surgery. Baseline histopathological characteristics and serum Tg levels off l-T(4) at first postsurgical evaluation can accurately predict the risk of relapse.