The interfascial thoracic wall blockades Pecs I and Pecs II are increasingly applied in breast and axillary surgery. Despite the clear anatomical demarcations depicted at their introduction, the clinical outcome is more variable than would be expected based upon the described anatomy. In order to elucidate factors that explain this variability, we evaluated the spread of each injection-medial Pecs I, lateral Pecs I, the deep injection of the Pecs II-separately. A correlation of in vivo landmarks and ultrasound images with ex vivo ultrasound, reconstructed anatomical planes, histology and magnetic resonance imaging. The medial Pecs I, similar to the sagittal infraclavicular block positioning with needle position medial to the pectoral branch of the thoracoacromial artery, reaches the medial and lateral pectoral nerves. The lateral Pecs I, below the lateral third of the clavicle at the level of the third rib with needle position lateral to the pectoral branch of the thoracoacromial artery, additionally spreads to the axilla and reaches the intercostobrachial nerve. The deep Pecs II injection spreads to the lateral cutaneous part of the III-VI intercostal nerves and reaches the long thoracic nerve. The variability of the Pecs anesthetic blockades is driven by the selected Pecs I approach as only the lateral approach stains the intercostobrachial nerve. The pectoral branch of the thoracoacromial artery can serve as the landmark to differentiate the needle position of the medial and lateral Pecs I block. Clin. Anat. 32:421-429, 2019. (c) 2019 Wiley Periodicals, Inc.