For whosoever shall do the will of my Father which is in heaven, the same is my brother, and sister, and mother.

People's New Testament

12:50 The same is my brother. Not those with fleshly ties, but those who do the will of his Father in heaven. Such become God's spiritual children, and thus become spiritually related to the Son of God. It will be observed that there is no hint of adoration of Mary, his mother, here, or elsewhere in the Scriptures. That she was immaculately born, as the Queen of Heaven and the Mother of God, is a Catholic fable.

Wesley's Notes

12:49-50 See the highest severity, and the highest goodness! Severity to his natural, goodness to his spiritual relations! In a manner disclaiming the former, who opposed the will of his heavenly Father, and owning the latter, who obeyed it.

Jamieson-Fausset-Brown Bible Commentary

50. For whosoever shall do the will of my Father which is in heaven, the same is my brother, and sister, and mother-that is, "There stand here the members of a family transcending and surviving this of earth: Filial subjection to the will of My Father in heaven is the indissoluble bond of union between Me and all its members; and whosoever enters this hallowed circle becomes to Me brother, and sister, and mother!"

Matthew Henry's Concise Commentary

12:46-50 Christ's preaching was plain, easy, and familiar, and suited to his hearers. His mother and brethren stood without, desiring to speak with him, when they should have been standing within, desiring to hear him. Frequently, those who are nearest to the means of knowledge and grace are most negligent. We are apt to neglect that which we think we may have any day, forgetting that to-morrow is not ours. We often meet with hinderances in our work from friends about us, and are taken off by care for the things of this life, from the concerns of our souls. Christ was so intent on his work, that no natural or other duty took him from it. Not that, under pretence of religion, we may be disrespectful to parents, or unkind to relations; but the lesser duty must stand by, while the greater is done. Let us cease from men, and cleave to Christ; let us look upon every Christian, in whatever condition of life, as the brother, sister, or mother of the Lord of glory; let us love, respect, and be kind to them, for his sake, and after his example.