Transcranial color-coded Duplex sonography (TCCS) has been used for the identification of cerebrovascular disorders. Recently, its value in the diagnosis of disorders of the brain parenchyma has been proposed. The object of this study was to determine systematically the echo pattern of the brain parenchyma and to compare conventional B-mode imaging with tissue harmonic imaging (THI). Transcranial sonography (TCS) was performed in 54 healthy individuals through the temporal bone window using conventional B-mode imaging and THI by two experienced investigators. Identification rates for several brain structures were assessed, and the quality of depiction of each method was graded semiquantitatively. In addition, several parts of the ventricular system and the basal cerebral cisterns were measured. Four subjects did not have an adequate bone window for transcranial examination. In the remaining people, the bone window was assessed to be adequate (59%) or excellent (33%). In the majority (> 80%), TCS allowed an unequivocal identification of various brain structures. Inter-rater variability of the assessments of tissue echogenicity and measurements of the ventricular width were found to be low for several structures (e.g., brainstem, thalamus, or 3rd ventricle). The echo pattern of brain tissue in THI is identical to that described for B-mode imaging. Using THI, contours of brain structures were typically visualized more clearly and the reproducibility of measurements was more consistent. In our experience, insonation of the contralateral lobes was limited when depths were higher than 12 cm using THI. In conclusion, TCS allowed the sonographic examination of the brain parenchyma in the majority of our subjects. THI substantially improves the identification of parenchymal structures when the depth is below 12 cm.