Multiple Myeloma: This is a common cause of multiple osteolytic lesions in the calvaria, characterized by the proliferation of malignant plasma cells in the bone marrow. The calvarial lesions are typically punched-out and well-defined on imaging.

Metastatic Disease: Metastases to the calvaria from various primary cancers (e.g., breast, lung, prostate) can present as multiple osteolytic lesions. The appearance can vary but often includes both lytic and blastic components.
Langerhans Cell Histiocytosis (LCH): LCH can cause multiple osteolytic lesions in the calvaria, especially in children and young adults. These lesions can be associated with soft tissue masses and may have a beveled edge appearance on radiographs.
Eosinophilic Granuloma: A form of LCH that typically presents with solitary or a few osteolytic lesions but can occasionally be multiple, especially in the context of multisystem disease.

Intracranial Malignancies with Calvarial Involvement: Certain primary brain tumors (e.g., meningiomas) or aggressive tumors (e.g., glioblastoma) can erode through the calvaria, mimicking osteolytic lesions. Missing these diagnoses could lead to delayed treatment of a potentially life-threatening condition.
Infections (e.g., Osteomyelitis, Abscesses): While less common, infections can cause lytic lesions in the calvaria, especially in immunocompromised patients. Prompt diagnosis is crucial for appropriate antimicrobial therapy.

Gorlin Syndrome (Nevoid Basal Cell Carcinoma Syndrome): Characterized by multiple basal cell carcinomas, odontogenic keratocysts, and skeletal abnormalities, including osteolytic lesions of the calvaria.
Calvarial Brown Tumors in Hyperparathyroidism: These are rare osteolytic lesions associated with hyperparathyroidism, which can affect the calvaria among other bones.
Calvarial Involvement in Sarcoidosis: Sarcoidosis can rarely cause osteolytic lesions in the calvaria, usually in the context of systemic disease.