I am making an Excel 2010 spreadsheet that may end up having 400 – 500 columns of data. Will a large number of columns like that be unstable?
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I will just give you an experience. Excel 2010 files with more than 80Mb of size will not even be loaded by Excel.
Remember Excel 2010 uses OpenXML by default as its file format, but MS recommends you save the file as an Excel Binary Workbook (.xlsb) if you have too many formulas in your speedsheet.
So considering the number of the columns check out the size of the file, if is not big, i think there is no problem.