Background: Several trace minerals have been shown to be associated with thyroid cancer. However, there is a paucity of data on the characteristics of thyroid nodules in different mineral rich regions of the Democratic Republic of Congo (DRC). The objective of this study is to establish the spectrum of thyroid nodules in different regions of the most mineral wealthy country in the world. Method: We conducted a cross-sectional study, performing descriptive statistics and logistic regression with a p value < 0.05 deemed of statistical significance. We enrolled 529 patients diagnosed with thyroid nodules between 2005 and 2019 in two of the richest provinces in minerals (Katanga and South Kivu) and the capital city, Kinshasa. Results: The mean age was 44.2±14.6 years with a female predominance, with a female to male ratio of 5.4. 66.5% of patients had a family history of thyroid disease. 74 patients had simple nodules, whereas 455 had multiple nodules. 87.7% of patients with nodules were euthyroid. The nodules mostly presented a solid structure (72.2%), hypoechogenicity (84.5%), a macronodule (59.8%), calcification (14.4%) and lymphadenopathy (15.5%). 22.3% of these nodules had a malignant character. The independent factors associated with this malignancy were age ≥60 years (aOR=2.81), Katanga as province of origin (aOR=8.19), solid echostructure (aOR=7.69), hypoechogenicity (aOR=14.19), macronodule (aOR=9.13), calcification (aOR=2.6) and the presence of adenopathy (aOR=6.94). Conclusion: By the way of this first of its kind study, we demonstrated that thyroid nodules were more likely to be malignant if found in patients originating from mineral rich region of Katanga. This high frequency of malignancy in mineral rich regions requires measures aimed at early detection in this population, lower threshold for suspicion of malignancy and adequate training of doctors involved in the management of these patients. This study paves the way for future, more extensive and well-funded studies to better understand the relationship of heavy metals and thyroid cancer incidence in the richest country in heavy metals in the world.