Atypical parathyroid adenoma (APA) is a rare cause of primary hyperparathyroidism (PHPT) and represents a diagnostic challenge since it is an intermediate form of parathyroid neoplasm of uncertain malignant potential with atypical histological features that require differential diagnosis of parathyroid carcinoma (PC). We present 2 cases of parathyroid crisis as a presentation of APA. The first case was that of a 56-year-old man with parathyroid crisis, constitutional syndrome, and anemia, with evidence of APA after en bloc resection, evolving with hungry bone syndrome after surgery and curation criteria at 6 months after parathyroidectomy (PTX). The second case was a 64-year-old woman with acute chronic kidney disease and parathyroid crisis, with evidence of APA after selective PTX and >50% reduction in parathyroid hormone levels after surgery; however, persistent PHPT at 6 months post-surgery was observed. These cases represented a diagnostic challenge due to their rare clinical presentation (parathyroid crisis), with a heterogeneous spectrum of target organ damage and infrequent symptoms (constitutional syndrome and acute chronic renal disease), in turn caused by a rare pathology (APA). The presentation of these patients may be indicative of PC; however, histopathological diagnosis is a key to the diagnosis of APA. The differential diagnosis of APA vs. PC in clinical practice is indispensable.