Introduction Thalamic space-occupying lesions (SOL) are considered challenging for microsurgical removal. Unfortunately, the pathological features of lesions occurring in the thalamic region are different with a wide variation in clinical behavior and outcome. Although microsurgery is still the gold standard in the management of these lesions through different approaches, questions remain whether surgery is feasible and safe in these patients and what are the alternatives? It is well known that stereotactic techniques may be favorable especially in cystic, small, multiple lesions and in combination with adjuvant therapy. Transventricular endoscopic approach is also an alternative technique to combine tumor biopsy and treatment of hydrocephalus. Aim of the study The identification of the different procedures for the management of thalamic SOL in respect to the age of the patient, the clinical condition, and the site of the lesion as well as its extent and pathology. Patients and methods This prospective study included 35 patients having thalamic lesions with a mean age of 27 years old who were treated with different approaches including microsurgical, stereotactic, and endoscopic approaches. The clinical outcome was assessed as the same, improved, deteriorated, or died in comparison to the initial clinical status, while the radiological control was measured as no gross residual, residual 10%. Chi-square test was used to test the association between two categorical variables. Results Thirty-five patients were included in this study, 20 were males and 15 were females. Eight cases were children, and 27 cases were adults. The most common clinical presentation was contralateral hemiparesis. The most common pathology was pilocytic astrocytoma. Radiological studies showed that the total thalamic type was the most common topographic variant and that 10 cases had hydrocephalus treated with CSF diversion procedures. For the definitive lesion, 2 cases underwent endoscopic biopsy and cystoventriculostomy and 18 cases had stereotactic technique in the form of biopsy, aspiration, and ommaya reservoir application, while 15 cases had microsurgery through different approaches with stereotactic technique preceding surgery in 2 of them. Conclusion The main factors involved in choosing the appropriate approach included nature of the lesion (solid or cystic, multiplicity), suspected pathological type, and diffusion tensor imaging. Abscesses are best treated with stereotaxy, while non-neoplastic cystic lesions (other than abscesses) related to the ventricles are best treated with endoscopy. For the remaining pathologies, maximum surgical removal is the best management. Best lesion control was provided by microsurgery. Trial registration ISRCTN 1380 registered 6/11/2018
