We introduce and study tetrahedron instantons, which can be realized in string theory by D1-branes probing a configuration of intersecting D7-branes in flat spacetime with a nonzero constant background B-field. Physically they capture instantons on C 3 in the presence of the most general intersecting codimention-two supersymmetric defects. Moreover, we construct the tetrahedron instantons as particular solutions of general instanton equations in noncommutative field theory. We analyze the moduli space of tetrahedron instantons and discuss the geometric interpretations. We compute the instanton partition function both via the equivariant localization on the moduli space of tetrahedron instantons and via the elliptic genus of the worldvolume theory on the D1-branes probing the intersecting D7-branes, obtaining the same result. The instanton partition function of the tetrahedron instantons lies between the higher-rank Donaldson-Thomas invariants on C 3 and the partition function of the magnificent four model, which is conjectured to be the mother of all instanton partition functions. Finally, we show that the instanton partition function admits a free field representation. 8 Future directions 38 A Open strings in the presence of the background B-field 41 B Two-dimensional supersymmetric gauge theory 44 B.1 N = (2, 2) supersymmetry 44 B.2 N = (0, 2) supersymmetry 46 C Elliptic genus of N = (0, 2) theories 48 D Jeffrey-Kirwan residue formula 50