In this report, we discuss the case of a 54-year-old patient attending our department with osteopenia, urolithiasis, significant hypercalciuria, and nephrocalcinosis. After the necessary complementary tests, an NGS (Next Generation Sequencing) for the main genes linked to 1α,25-dihydroxyvitamin D and 25-vitamin D identified a homozygous pathogenic variant associated with loss of function in the CYP24A1 gene. Homozygous pathogenic variants associated with loss of function in this gene result in a defective 24-hydroxylase, leading to increased levels of 1α,25-dihydroxyvitamin D. It can be challenging to clinically differentiate CYP24A1 deficiency cases from other hypercalcemic/hypercalciuric conditions associated with higher levels of 1α,25-dihydroxyvitamin D and suppressed PTH, such as lymphoma and granulomatous diseases, but there can be some major indicators to focus on for diagnosis. We discuss the main therapeutic choices for treating this group of patients, where fluconazole emerges as a P450 inhibitor with a better profile than ketoconazole, which has been used and studied recently to reduce serum calcium levels and urinary calcium excretion in patients with CYP24A1 pathogenic variants.