The curve fitting toolbox can help you deal with irregular data. Here I make a noisy surface, approximate it using polynomials, subtract the two, and then display the noise. There is a neat surface fitting GUI tool called "sftool" as well.
x = rand(65000,1); y = rand(65000,1); z0 = log(1+x).*sin(3*y); z = z0 + 0.05*randn(size(z0));
figure plot3(x,y,z,'k.','markersize',1); hold on; F = fit([x y],z,'poly55'); plot(F); alpha 0.5;
figure subplot(211) plot3(x,y,F(x,y) - z,'.','markersize',1); subplot(212) plot(F(x,y) - z);