Post-therapeutic whole-body scan (WBS) with I-131 has been widely used for the follow-up of patients with well-differentiated thyroid cancer (DTC). Although the sensitivity of WBS with I-131 in detection of functioning thyroid tissues is high, its specificity is low. So, a further evaluation is required in cases of unexpected findings. The purpose of the study was to demonstrate that awareness of the potential pitfalls of WBS in DTC, knowledge of physiology and characteristics of radioiodine uptake, and correlation with other imaging modalities are needed to avoid incorrect management of patients with DTC. This is a case report of a 49-year-old woman with an unexpected area of increased I-131 uptake in the posterior lower chest, which was finally diagnosed as a pleuropericardial cyst. Due to the false-positive uptake of I-131 in the chest, an accurate interpretation of the scintigraphic findings should be made.